0019-9567/78/0019-0146$02.00/0
Vol. 19, No. 1
INFECTION AND IMMUNITY, Jan. 1978, p. 146-151
Printed in U.S.A.
Copyright © 1978 American Society for Microbiology
Effect of L1210 Leukemia on the Susceptibility of Mice to Candida albicans Infections JUDITH A. JOHNSON,1 BENJAMIN H. S. LAU,1 2* ROBERT L. NUTTER,"12 JAMES M. SLATER 2 AND CHARLES E. WINTER' Departments of Microbiology' and Radiology,2 School ofMedicine, Loma Linda University, Loma Linda, California 92354 Received for publication 29 July 1977
This study was carried out to determine whether animals bearing L1210 leukemia were more susceptible to candida infection in the absence of immunosuppression and to determine also if the L1210 cells suppressed the inflammatory response of the animal host. Systemic infection was studied by intravenous injection of Candida albicans and checking for the number of candida organisms cultured from the blood and the kidneys. Localized infection was studied by intramuscular injection of C. albicans into the thighs and measuring the changes in the thigh size. Compared with tumor-free controls, the intravenous injection resulted in higher counts of C. albicans from the blood and the kidneys of tiumor-bearing animals. No significant difference in the localized swelling was noted between tumor- and nontumor-bearing mice with respect to intramuscular injection of C. albicans. The results thus indicate that L1210 leukemia increases susceptibility of tumor-bearing animals to systemic candida infection. L1210 cells were shown to reduce the accumulation of neutrophils and to suppress the inflammatory reaction elicited by C. albicans.
One of the major causes of morbidity and mortality in cancer patients is opportunistic fungal infections (8, 16, 20). This is especially true with leukemias and lymphomas (5, 10, 13, 24). Of the fungal agents, the most commonly found in association with cancer are Aspergillus, Candida, and Mucor (8,16). Disseminated infections are more frequently encountered than localized infections (13, 28). However, it is uncertain whether the increase in the incidence of infections is due to lowered resistance caused by cancer or to the anticancer therapy which the patients receive (8, 16, 20, 28). Several factors have been suggested to increase host susceptibility to infections in cancer patients, such as decreased levels of mature granulocytes (1), neutrophils with decreased ability to migrate to areas of inflammation (9), and decreased capacity of leukocytes to kill ingested microorganisms (26). Using animal models, studies have shown that several tumor systems are capable of suppressing the cellular inflammatory response (3, 6). The increased susceptibility to infection may be associated with this defective inflammatory response. Considering that most opportunistic infections occur with leukemias and lymphomas (28), we selected the transplantable L1210 murine leukemia as a model to determine the effects of a malignancy on the susceptibility of mice to
infections. The L1210 lymphocytic leukemia was originally obtained in DBA mice after skin paintings with methylcholanthrene (12). The tumor grows progressively in DBA mice and F1 hybrids, and the length of survival is 10 to 12 days. While several virus-induced leukemias have been shown to depress the immune system (7), no depression of the lymphocyte-mediated immune responses until the terminal phase of the disease has been demonstrated with L1210 leukemia (2, 25). Recently, however, North et al. demonstrated that murine tumors subverted host defense mechanisms by suppressing macrophagemediated resistance (17, 18). The purpose of this study was to determine whether animals bearing L1210 leukemia were more susceptible to candida infections in the absence of lymphocyte-associated immunosuppression and to determine also if the L1210 tumor suppressed the inflammatory response of the animal host.
MATERLALS AND METHODS Animals. Male and female DBA/2 mice, weighing 18 to 22 g, were obtained from the Simonsen Laboratories, Gilroy, Calif. They were kept under normal laboratory conditions and were fed Purina Laboratory Chow and tap water ad libitum. Tumor transplantation. L1210 tumor was obtained from W. T. Chu, Loma Linda University Med146
VOL. 19, 1978
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L1210 LEUKEMIA AND C. ALBICANS INFECTIONS
ical Center, Loma Linda, Calif., and maintained in the laboratory by weekly intraperitoneal (i.p.) injection with 5 x 105 cells in DBA/2 mice. For inoculation of experimental animal ascites obtained from a freshly killed tumor-bearing animal was diluted with cold (400) sterile saline to contain 2 x 101 cells per ml. The viability was determined with trypan blue and maintained at 95% level in all experiments. Experimental animals were injected i.p. with 0.25 ml of suspension containing 5 x 103 viable cells unless indicated otherwise. Candida albicanu C. albicans culture was obtained from the Clinical Laboratory of Loma Linda University Medical Center. It was maintained on Sabouraud dextrose agar (Difco Laboratories, Detroit, Mich.) plates at 37°C. Suspensions were made from agar, washed, and diluted with sterile saline to the desired concentration. The stock suspension was aliquoted and stored at -70°C until needed. When needed, the suspension was thawed at 37°C, and colony counts were made to ascertain the concentration and viability. Suspensions stored at -70°C showed no loss of viability within 6 months. The 50% lethal dose of this strain of C. albicans for DBA/2 mice was 1.75 x 105 by intravenous (i.v.) injection. Infections. For systemic infections, four of the eight groups of mice were transplanted with L1210 cells, whereas the other four groups were transplanted with an equal number of normal lymphocytes from the spleen of normal DBA/2 mice. The latter four groups were included to test for the specificity of L1210 cells. The four groups of mice with either L1210 cells or normal lymphocytes received i.v. injections in the tail vein with 0.2 ml of culture suspension containing 1 x 106 C. albicans on the same day as and 1, 3, and 6 days after tumor or lymphocyte transplant. An additional group of control animals without L1210 or lymphocyte transplant received C. albicans only. Three days after the C. albicans injection, blood cultures were made with the pour-plate technique using 0.5 ml of blood obtained from the inferior vena cava in 14.5 ml of melted Sabouraud dextrose agar. The animals were then sacrificed, and the kidneys were removed and macerated. Dilutions of kidney suspension were made in sterile saline. Two-tenths mifliliter of each dilution, in duplicate, was streaked onto Sabouraud dextrose agar plates for colony counts. The colonies of both blood and kidney cultures were determined after 48 h of incubation at 370C. For localized infections, four groups of mice were used. Three groups with tumor transplants were injected with 0.2 ml of culture suspension containing 1 x 108 C. albicans intramuscularly (im.) into the right thighs, and 0.2 ml of sterile saline were injected i.m. into the left thighs on the same day as and 2 and 5 days after tumor transplant. The fourth group of tumor-free controls was similarly injected. The thighs were measured daily with sliding calipers. The injection of C. albicans causes an enlargement of the thigh that serves as a measured indicator of the course of the infection (19). Inflammatory reaction. Acute inflammatory reaction was induced in mice by i.p. injection with 3 ml of RPMI 1640 medium (6). To determine whether the L1210 cells prevented the inflammatory response, 5 x
10i L1210 cells in 3 ml of RPMI 1640 medium were injected i.p. into the mice. At 2-h intervals after the injection, a group of mice was killed, and impression smears were made from the peritoneal cavity. The smears were air dried, fixed in methanol for 2 min, and stained with Giemsa stain (Harleco, Philadelphia, Pa.) for 45 min. A count of 500 cells was made, and the percentage of neutrophils was recorded. Controls injected with RPMI medium containing 5 x 101 normal lymphocytes from either spleen or kidney of DBA mice were run in parallel. In another experiment, the effect of L1210 cells on the thigh size in response to C. albicans injection was studied. Two groups of mice were used. In the first group, the left thigh of each mouse was injected i.m. with 108 C. albicans cells in 0.2 ml of sterile saline, and the right thigh was injected i.m. with the saline only. In the second group, the left thigh of the mouse was injected i.m. with 1 x 108 C. albicans celLs in 0.2 ml of saline, and the right thigh was injected i.m. with a mixture of 5 x 108 L1210 cells and 1 x 101 C. albicans cells in 0.2 ml of saline. The thighs were measured daily with sliding calipers.
RESULTIS Effect of L1210 leukemia on mice with i.v. inJections of C albicanm. Figure 1 shows the resuts of blood cultures obtained from the nine groups of mice. The mean colony count of control mice without either L1210 or normal lymphocyte tansplant was 1.14 x 105/0.5 ml of blood. Comparisons were made by considering the mean colony count of this control group as 100%. The mean colony counts of 70, 54, 83, and 132% of that of the controls were obtained with w I-J
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DAYS FIG. 1. Effect of L1210 and normal lymphocyte transplant on the recovery of C. albicans from blood. Comparsons were made with controls without transplant. Open bars represent groups transplanted with normal lymphocytes and ijected iv. with C. albicans at days 0, 1, 3, and 6. Blackened bars represent groups transplanted with L1210 twmor.
148
JOHNSON ET AL.
INFECT. IMMUN.
groups of mice receiving normal lymphocyte transplant and injected with C. albicans on the same day as (day 0) and 1, 3, and 6 days after the transplant, respectively. These differences were not statistically significant compared with controls without lymphocyte transplant. The animals with L1210 tumor had increases of colony counts of blood cultures on days 0, 3, and 6 when compared with the controls. The increases on days 0 and 6 were statistically significant (P < 0.01). The results of kidney cultures are shown in Fig. 2. The mean colony count of the group without either L1210 or normal lymphocyte transplant was 3.41 x 104. The groups of mice injected i.v. with C. albicans on the same day as and 1, 3, and 6 days after normal lymphocyte transplant had mean colony counts of 141, 131, 133, and 147% of that of the control group, respectively. These increases were, however, not statistically significant. The groups of mice injected with C. albicans on the same day as and 1, 3, and 6 days after L1210 tumor transplant had mean colony counts of 400, 884, 468, and 179% of that of the controls, respectively. The increases on days 0, 1, and 3 were statistically significant compared with the controls (P < 0.01). Effect of L1210 leukemia on mice with i.m. injections of C. albicans. In this experiment, the increase of thigh size following C. albicans injection was used as a measurable indicator of localized infection (19). There was no significant increase in thigh size in tumor900
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FIG. 2. Effect of L1210 and normal lymphocyte transplant on the recovery of C. albicans from kidneys. Comparisons were made with controls without transplant. Open bars represent groups transplanted with normal lymphocytes and injected i.v. with C. albicans at days 0, 1, 3, and 6. Blackened bars represent groups transplanted with L1210 tumor.
bearing mice compared with tumor-free controls, regardless of the time intervals between tumor transplant and C. albicans injection. More rapid decrease in thigh size was actually noted in the tumor-bearing animals than in tumor-free controls (Table 1). Effect of L1210 cells on the inflammatory response. There was a steady increase in the percentage of neutrophils following i.p. injection of RPMI medium into the mice (Fig. 3). The peak response was noted between 6 and 8 h after the injection. The injection of normal lymphocytes in RPMI medium elicited essentially a similar neutrophilic response. The injection of L1210 cells in RPMI medium elicited only a slight increase of the neutrophils. The effect of L1210 cells on the inflammatory response elicited by C. albicans is shown in Table 2. Animals which received C. albicans injections in the left thigh and saline in the right thigh demonstrated significant increase in the thigh size due to C. albicans injections. The group of mice which received C. albicans in the left thighs and the mixture of C. albicans and L1210 cells in the right thighs showed approximately the same magnitude of increase of thigh size on day 1. The thighs injected with C. albicans only continued to increase in size on days 4 and 7, whereas the thighs injected with the mixture of C. albicans and L1210 showed no further increase in size.
DISCUSSION Opportunistic candida infections occur in cancer patients and in compromised host. Several factors which predispose an individual to candidiasis have been documented, such as broadspectrum antibiotics (23), corticosteroids and anti-inflammatory agents (14,22), and prolonged anesthesia (11). In the case of cancer patients, it is uncertain whether candidiasis results primarily from an intrinsic defect in the host defense caused by the malignancy or from the therapy which the patients receive. Since the opportunistic fungal infection is more frequently seen with leukemia and lymphoma patients (28), the murine lymphocytic L1210 leukemia was selected as a model. This model has the advantage in that no immunosuppression in the early stage of the tumor has been reported, whereas virus-induced leukemias often show concurrent suppression of the immune response (2, 7, 25). The data presented in this paper indicate that L1210 leukemia increases the susceptibility of tumor-bearing animals to systemic (i.v.) infection of C. albicans. Transplantation with nornal lymphocytes did not affect significantly the recovery of C. albi-
L1210 LEUKEMIA AND C. ALBICANS INFECTIONS
VOL. 19, 1978
TABLE 1. Thigh sizes of mice inoculated with C. albicansa Mean sizec of thigh (mm) at days: Days relative to tumor trans7-8 1-2 plantb 3-4 5-6
149
9-10
5.8±0.2 6.9±0.1 6.8±0.2 6.9±0.1 6.7 ± 0.2 5.4 ± 0.1 7.0 ± 0.1 5.1±0.3 5.3±0.2 6.9 ± 0.3 7.4 ± 0.1 6.9 ± 0.1 6.8 ± 0.1 Control (without tumor) a C. albicans celLs were injected i.m. into the left thigh; diluent alone (0.2 ml of saline) was injected into the right thigh. The thigh with saline injection was consistently
Vol. 19, No. 1
INFECTION AND IMMUNITY, Jan. 1978, p. 146-151
Printed in U.S.A.
Copyright © 1978 American Society for Microbiology
Effect of L1210 Leukemia on the Susceptibility of Mice to Candida albicans Infections JUDITH A. JOHNSON,1 BENJAMIN H. S. LAU,1 2* ROBERT L. NUTTER,"12 JAMES M. SLATER 2 AND CHARLES E. WINTER' Departments of Microbiology' and Radiology,2 School ofMedicine, Loma Linda University, Loma Linda, California 92354 Received for publication 29 July 1977
This study was carried out to determine whether animals bearing L1210 leukemia were more susceptible to candida infection in the absence of immunosuppression and to determine also if the L1210 cells suppressed the inflammatory response of the animal host. Systemic infection was studied by intravenous injection of Candida albicans and checking for the number of candida organisms cultured from the blood and the kidneys. Localized infection was studied by intramuscular injection of C. albicans into the thighs and measuring the changes in the thigh size. Compared with tumor-free controls, the intravenous injection resulted in higher counts of C. albicans from the blood and the kidneys of tiumor-bearing animals. No significant difference in the localized swelling was noted between tumor- and nontumor-bearing mice with respect to intramuscular injection of C. albicans. The results thus indicate that L1210 leukemia increases susceptibility of tumor-bearing animals to systemic candida infection. L1210 cells were shown to reduce the accumulation of neutrophils and to suppress the inflammatory reaction elicited by C. albicans.
One of the major causes of morbidity and mortality in cancer patients is opportunistic fungal infections (8, 16, 20). This is especially true with leukemias and lymphomas (5, 10, 13, 24). Of the fungal agents, the most commonly found in association with cancer are Aspergillus, Candida, and Mucor (8,16). Disseminated infections are more frequently encountered than localized infections (13, 28). However, it is uncertain whether the increase in the incidence of infections is due to lowered resistance caused by cancer or to the anticancer therapy which the patients receive (8, 16, 20, 28). Several factors have been suggested to increase host susceptibility to infections in cancer patients, such as decreased levels of mature granulocytes (1), neutrophils with decreased ability to migrate to areas of inflammation (9), and decreased capacity of leukocytes to kill ingested microorganisms (26). Using animal models, studies have shown that several tumor systems are capable of suppressing the cellular inflammatory response (3, 6). The increased susceptibility to infection may be associated with this defective inflammatory response. Considering that most opportunistic infections occur with leukemias and lymphomas (28), we selected the transplantable L1210 murine leukemia as a model to determine the effects of a malignancy on the susceptibility of mice to
infections. The L1210 lymphocytic leukemia was originally obtained in DBA mice after skin paintings with methylcholanthrene (12). The tumor grows progressively in DBA mice and F1 hybrids, and the length of survival is 10 to 12 days. While several virus-induced leukemias have been shown to depress the immune system (7), no depression of the lymphocyte-mediated immune responses until the terminal phase of the disease has been demonstrated with L1210 leukemia (2, 25). Recently, however, North et al. demonstrated that murine tumors subverted host defense mechanisms by suppressing macrophagemediated resistance (17, 18). The purpose of this study was to determine whether animals bearing L1210 leukemia were more susceptible to candida infections in the absence of lymphocyte-associated immunosuppression and to determine also if the L1210 tumor suppressed the inflammatory response of the animal host.
MATERLALS AND METHODS Animals. Male and female DBA/2 mice, weighing 18 to 22 g, were obtained from the Simonsen Laboratories, Gilroy, Calif. They were kept under normal laboratory conditions and were fed Purina Laboratory Chow and tap water ad libitum. Tumor transplantation. L1210 tumor was obtained from W. T. Chu, Loma Linda University Med146
VOL. 19, 1978
147
L1210 LEUKEMIA AND C. ALBICANS INFECTIONS
ical Center, Loma Linda, Calif., and maintained in the laboratory by weekly intraperitoneal (i.p.) injection with 5 x 105 cells in DBA/2 mice. For inoculation of experimental animal ascites obtained from a freshly killed tumor-bearing animal was diluted with cold (400) sterile saline to contain 2 x 101 cells per ml. The viability was determined with trypan blue and maintained at 95% level in all experiments. Experimental animals were injected i.p. with 0.25 ml of suspension containing 5 x 103 viable cells unless indicated otherwise. Candida albicanu C. albicans culture was obtained from the Clinical Laboratory of Loma Linda University Medical Center. It was maintained on Sabouraud dextrose agar (Difco Laboratories, Detroit, Mich.) plates at 37°C. Suspensions were made from agar, washed, and diluted with sterile saline to the desired concentration. The stock suspension was aliquoted and stored at -70°C until needed. When needed, the suspension was thawed at 37°C, and colony counts were made to ascertain the concentration and viability. Suspensions stored at -70°C showed no loss of viability within 6 months. The 50% lethal dose of this strain of C. albicans for DBA/2 mice was 1.75 x 105 by intravenous (i.v.) injection. Infections. For systemic infections, four of the eight groups of mice were transplanted with L1210 cells, whereas the other four groups were transplanted with an equal number of normal lymphocytes from the spleen of normal DBA/2 mice. The latter four groups were included to test for the specificity of L1210 cells. The four groups of mice with either L1210 cells or normal lymphocytes received i.v. injections in the tail vein with 0.2 ml of culture suspension containing 1 x 106 C. albicans on the same day as and 1, 3, and 6 days after tumor or lymphocyte transplant. An additional group of control animals without L1210 or lymphocyte transplant received C. albicans only. Three days after the C. albicans injection, blood cultures were made with the pour-plate technique using 0.5 ml of blood obtained from the inferior vena cava in 14.5 ml of melted Sabouraud dextrose agar. The animals were then sacrificed, and the kidneys were removed and macerated. Dilutions of kidney suspension were made in sterile saline. Two-tenths mifliliter of each dilution, in duplicate, was streaked onto Sabouraud dextrose agar plates for colony counts. The colonies of both blood and kidney cultures were determined after 48 h of incubation at 370C. For localized infections, four groups of mice were used. Three groups with tumor transplants were injected with 0.2 ml of culture suspension containing 1 x 108 C. albicans intramuscularly (im.) into the right thighs, and 0.2 ml of sterile saline were injected i.m. into the left thighs on the same day as and 2 and 5 days after tumor transplant. The fourth group of tumor-free controls was similarly injected. The thighs were measured daily with sliding calipers. The injection of C. albicans causes an enlargement of the thigh that serves as a measured indicator of the course of the infection (19). Inflammatory reaction. Acute inflammatory reaction was induced in mice by i.p. injection with 3 ml of RPMI 1640 medium (6). To determine whether the L1210 cells prevented the inflammatory response, 5 x
10i L1210 cells in 3 ml of RPMI 1640 medium were injected i.p. into the mice. At 2-h intervals after the injection, a group of mice was killed, and impression smears were made from the peritoneal cavity. The smears were air dried, fixed in methanol for 2 min, and stained with Giemsa stain (Harleco, Philadelphia, Pa.) for 45 min. A count of 500 cells was made, and the percentage of neutrophils was recorded. Controls injected with RPMI medium containing 5 x 101 normal lymphocytes from either spleen or kidney of DBA mice were run in parallel. In another experiment, the effect of L1210 cells on the thigh size in response to C. albicans injection was studied. Two groups of mice were used. In the first group, the left thigh of each mouse was injected i.m. with 108 C. albicans cells in 0.2 ml of sterile saline, and the right thigh was injected i.m. with the saline only. In the second group, the left thigh of the mouse was injected i.m. with 1 x 108 C. albicans celLs in 0.2 ml of saline, and the right thigh was injected i.m. with a mixture of 5 x 108 L1210 cells and 1 x 101 C. albicans cells in 0.2 ml of saline. The thighs were measured daily with sliding calipers.
RESULTIS Effect of L1210 leukemia on mice with i.v. inJections of C albicanm. Figure 1 shows the resuts of blood cultures obtained from the nine groups of mice. The mean colony count of control mice without either L1210 or normal lymphocyte tansplant was 1.14 x 105/0.5 ml of blood. Comparisons were made by considering the mean colony count of this control group as 100%. The mean colony counts of 70, 54, 83, and 132% of that of the controls were obtained with w I-J
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DAYS FIG. 1. Effect of L1210 and normal lymphocyte transplant on the recovery of C. albicans from blood. Comparsons were made with controls without transplant. Open bars represent groups transplanted with normal lymphocytes and ijected iv. with C. albicans at days 0, 1, 3, and 6. Blackened bars represent groups transplanted with L1210 twmor.
148
JOHNSON ET AL.
INFECT. IMMUN.
groups of mice receiving normal lymphocyte transplant and injected with C. albicans on the same day as (day 0) and 1, 3, and 6 days after the transplant, respectively. These differences were not statistically significant compared with controls without lymphocyte transplant. The animals with L1210 tumor had increases of colony counts of blood cultures on days 0, 3, and 6 when compared with the controls. The increases on days 0 and 6 were statistically significant (P < 0.01). The results of kidney cultures are shown in Fig. 2. The mean colony count of the group without either L1210 or normal lymphocyte transplant was 3.41 x 104. The groups of mice injected i.v. with C. albicans on the same day as and 1, 3, and 6 days after normal lymphocyte transplant had mean colony counts of 141, 131, 133, and 147% of that of the control group, respectively. These increases were, however, not statistically significant. The groups of mice injected with C. albicans on the same day as and 1, 3, and 6 days after L1210 tumor transplant had mean colony counts of 400, 884, 468, and 179% of that of the controls, respectively. The increases on days 0, 1, and 3 were statistically significant compared with the controls (P < 0.01). Effect of L1210 leukemia on mice with i.m. injections of C. albicans. In this experiment, the increase of thigh size following C. albicans injection was used as a measurable indicator of localized infection (19). There was no significant increase in thigh size in tumor900
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FIG. 2. Effect of L1210 and normal lymphocyte transplant on the recovery of C. albicans from kidneys. Comparisons were made with controls without transplant. Open bars represent groups transplanted with normal lymphocytes and injected i.v. with C. albicans at days 0, 1, 3, and 6. Blackened bars represent groups transplanted with L1210 tumor.
bearing mice compared with tumor-free controls, regardless of the time intervals between tumor transplant and C. albicans injection. More rapid decrease in thigh size was actually noted in the tumor-bearing animals than in tumor-free controls (Table 1). Effect of L1210 cells on the inflammatory response. There was a steady increase in the percentage of neutrophils following i.p. injection of RPMI medium into the mice (Fig. 3). The peak response was noted between 6 and 8 h after the injection. The injection of normal lymphocytes in RPMI medium elicited essentially a similar neutrophilic response. The injection of L1210 cells in RPMI medium elicited only a slight increase of the neutrophils. The effect of L1210 cells on the inflammatory response elicited by C. albicans is shown in Table 2. Animals which received C. albicans injections in the left thigh and saline in the right thigh demonstrated significant increase in the thigh size due to C. albicans injections. The group of mice which received C. albicans in the left thighs and the mixture of C. albicans and L1210 cells in the right thighs showed approximately the same magnitude of increase of thigh size on day 1. The thighs injected with C. albicans only continued to increase in size on days 4 and 7, whereas the thighs injected with the mixture of C. albicans and L1210 showed no further increase in size.
DISCUSSION Opportunistic candida infections occur in cancer patients and in compromised host. Several factors which predispose an individual to candidiasis have been documented, such as broadspectrum antibiotics (23), corticosteroids and anti-inflammatory agents (14,22), and prolonged anesthesia (11). In the case of cancer patients, it is uncertain whether candidiasis results primarily from an intrinsic defect in the host defense caused by the malignancy or from the therapy which the patients receive. Since the opportunistic fungal infection is more frequently seen with leukemia and lymphoma patients (28), the murine lymphocytic L1210 leukemia was selected as a model. This model has the advantage in that no immunosuppression in the early stage of the tumor has been reported, whereas virus-induced leukemias often show concurrent suppression of the immune response (2, 7, 25). The data presented in this paper indicate that L1210 leukemia increases the susceptibility of tumor-bearing animals to systemic (i.v.) infection of C. albicans. Transplantation with nornal lymphocytes did not affect significantly the recovery of C. albi-
L1210 LEUKEMIA AND C. ALBICANS INFECTIONS
VOL. 19, 1978
TABLE 1. Thigh sizes of mice inoculated with C. albicansa Mean sizec of thigh (mm) at days: Days relative to tumor trans7-8 1-2 plantb 3-4 5-6
149
9-10
5.8±0.2 6.9±0.1 6.8±0.2 6.9±0.1 6.7 ± 0.2 5.4 ± 0.1 7.0 ± 0.1 5.1±0.3 5.3±0.2 6.9 ± 0.3 7.4 ± 0.1 6.9 ± 0.1 6.8 ± 0.1 Control (without tumor) a C. albicans celLs were injected i.m. into the left thigh; diluent alone (0.2 ml of saline) was injected into the right thigh. The thigh with saline injection was consistently
