255 the possibility of developing an effective means for suppressing the immune response in vivo may be increased.
synthetic,
Courtauld Institute of Biochemistry, Middlesex Hospital Medical School, London W1P 5PR
A. D. SMITH W. M. TSANG C. WEYMAN J. BELIN
VASOACTIVE INTESTINAL POLYPEPTIDE
SIR,—Dr Larsson (July 17, p. 149) has confirmed the findings of neural vasoactive intestinal polypeptide (v.i.p.) by our
group’
ference does exist, it seems, contrary to Godfrey’s finding, that the disease is more common in areas where parasitic infestations are rampant, and where ascariasis may reach a prevalence of 90-100% of all children. Furthermore, a common occurrence was the coexistence of both conditions in the same
patient. While we do not believe that a causal connection exists between parasitosis and asthma, there is also clearly no protective effect of the parasitosis either. If any relation does exist between the two conditions, it is a direct rather than an inverse one.
Nassr Pædiatric Hospital, Gaza (via Israel)
v.i.p.
is
v.i.p.
cells
can
be found in the gut mucosa.34Furthermore
v.i.p.-secreting apudomas are not of neural origin.4 The suggestion that diarrhoea may be caused by agents other than v.i.p. seems self-evident. Indeed, a third of gastrinoma patients have troublesome diarrhoea, and this feature is also seem in the glucagonoma syndromedespite normal v.i.p. and in many cases normal pancreatic polypeptide (P.P.) levels.6 It is possible that P.P. may be associated with diarrhoea, though many patients with high plasma-p.p. values (e.g., with insulinomas) have no diarrhoea.6 We are studying a patient with diarrhoea, normal v.i.p., and high plasma-p.p. produced by hepatic metastases of a pancreatic P.P.-oma, and it is indeed possible that P.P. is responsible for the clinical symptoms. That v.i.p. is responsible for diarrhoea of v.i.p.-omas is incontrovertible. Infusions of v.i.p. in pigs producing similar blood levels result in severe diarrhcea.7 A third of pancreatic v.i.p.-omas
MACROPHAGES v. CANCER
most
with massive diarrhoea have absent tumour P.P. cells and normal plasma P.P. levels.6 Ganglioneuromas producing v.i.p. and 9 watery diarrhoea* are never associated with excess P.P. production. Departments of Histochemistry and Medicine, Royal Postgraduate Medical School, London W12
melanoma’ and with cancer of the prostate,2have emphasised the importance of macrophages in this form of immunotherapy. B.C.G. contact suppression of tumours is a hostmediated response since the organisms are not directly cyto-
cutaneous
toxic for
tumour
cells, but
treatment
is successful in animals
lacking full lymphocyte competence. Thus, B.C.G. contact therapy of syngeneically transplanted rat tumours is successful even in immunosuppressed animals,3 4 and rat tumours xenografted to athymic "nude" mice may be prevented from FACILITATION OF B.C.G. CONTACT SUPPRESSION OF HEPATOMA
D23
BY
SYNGENEIC MACROPHAGES
S. R. BLOOM A. G. EVERSON PEARSE
Strip. In Gaza asthma is an extremely common disease among both children and adults. While no exact figures exist concerning its incidence in the population, it is among the most frequent diagnoses made in the outpatient clinics and emergency room of our hospital, with a frequency reaching 10—20% of all children examined. In contrast with Godfrey’s findings, no significant difference in the incidence of the disease could be seen among children from city, village, or refugee camps. If any difM. G., Bloom, S. R., Polak, J. M., Albyquerque, R. H., Modlin, I., Pearse, A G. E. Lancet, 1976, i, 991. 2 Said, S I., Rosenberg, R. N. Science, 1976, 192, 907. 3. Polak, J. M., Pearse, A. G. E., Garaud, J.-C., Bloom, S. R. Gut, 1974, 15,
Bryant,
720. 4. Bloom, S
SIR,-Your editorial (July 3, p. 27) draws attention to the paucity of knowledge concerning the role of macrophages both in immunosurveillance and in immunotherapy of cancer. Recent results, from this and other laboratories, of investigations on the mechanism of action ofB.c.G. regionally applied to tumour deposits, such as has been well described clinically with
J. M. POLAK
IgE, PARASITES, AND ALLERGY SIR,—Iwas astonished to realise that a generalisation such as the one which appears in your editorial of April 24 (p. 894}-"there is evidence for an inverse relation between parasites and allergy: asthma and hay fever are rare in parts of the world where the population is heavily parasitised"-was based uniquely on the findings of Godfrey in the Gambia.’° While this may be true in the Gambia, it certainly is not in the Gaza
1.
E. E. LASCH
subsequently by Said and Rosenberg.2 However, not only a neural peptide, for numerous endocrine
and
R., Polak, J. M. in Gastrointestinal Hormones (edited by J. C. Thompson),p. 635. Austin, Texas, 1975. 5. Mallinson, C. M., Bloom, S. R., Warin, A. P., Salmon, P. R., Cox, B. Lancet, 1974, ii, 1. 6 Polak. J M , Bloom, S. R., Adrian, T. E., Heitz, Ph., Bryant, M. G., Pearse, A G. E. ibid. 1976, i, 328. 7 Bloom. S R., Mitchell, S. J., Modlin, I. (Unpublished). 8 Swift, P. G. F., Bloom, S. R., Harris, F. Archs Dis. Childh. 1975, 50, 896. 9 Bloom, S. R., Polak, J. M., Pearse, A. G. E. Lancet, 1973, ii, 14. 10 Godfrey. R C Clin. Allergy, 1975, 5, 201.
*Glaxo percutaneous
vaccine B.P., 3x10’ viable units/mg organisms, representing approximately 20% viability.
moist
weight
of
type of B.C.G. therapy.’ In contrast, treatment of animals with particulate silica, of a type known to be selectively toxic for macrophages, abrogates B.C.G.-mediated tumour contact suppression both in rats6 and athymic mice,6 indicating that macrophages play a primary and important role in this type of local therapy. Furthermore, whilst transplanted rat tumours normally contain a proportion of host macrophages, varying widely between tumour types, there is a distinct correlation between the maximum number of cells of each tumour that can be suppressed by contact with B.C.G. and the extent of its host macrophage infiltration.8 Thus, tumours containing 25-30% macrophages (e.g., chemically induced sarcomas) are highly susceptible to B.c.G. therapy, whereas those containing only 2-3% macrophages (e.g., mammary carcinomas) are less responsive. Most importantly, our findings
growth by this
1.
D. L., Eilber, F. R., Holmes, E. C., Cancer Immun. Immunother. 1976, 1, 93.
Morton,
Sparks,
F.
C., Ramming, K. P.
Merrin, C., Han, T, Klein, E., Wajsman, Z., Murphy, G. P Cancer Chemother. Rep. 1975, 59, 157. 3 Pimm, M. V., Baldwin, R. W Br J. Cancer (in the press). 4. Moore, M, Lawrence, N., Nisbet, N. W. Int. J Cancer, 1975, 15, 891. 5 Pimm, M. V, Baldwin, R. W. Nature, 1975, 254, 77. 6. Hopper, D. G, Pimm, M. V., Baldwin, R. W. Cancer Immun. Immunother. 1976, 1, 143. Chassoux, D., Salomon, J.-C Int J. Cancer, 1975, 16, 515. 8 Baldwin, R. W. Transplant. Rev. 1976, 28, 62.
2
7
synthetic,
Courtauld Institute of Biochemistry, Middlesex Hospital Medical School, London W1P 5PR
A. D. SMITH W. M. TSANG C. WEYMAN J. BELIN
VASOACTIVE INTESTINAL POLYPEPTIDE
SIR,—Dr Larsson (July 17, p. 149) has confirmed the findings of neural vasoactive intestinal polypeptide (v.i.p.) by our
group’
ference does exist, it seems, contrary to Godfrey’s finding, that the disease is more common in areas where parasitic infestations are rampant, and where ascariasis may reach a prevalence of 90-100% of all children. Furthermore, a common occurrence was the coexistence of both conditions in the same
patient. While we do not believe that a causal connection exists between parasitosis and asthma, there is also clearly no protective effect of the parasitosis either. If any relation does exist between the two conditions, it is a direct rather than an inverse one.
Nassr Pædiatric Hospital, Gaza (via Israel)
v.i.p.
is
v.i.p.
cells
can
be found in the gut mucosa.34Furthermore
v.i.p.-secreting apudomas are not of neural origin.4 The suggestion that diarrhoea may be caused by agents other than v.i.p. seems self-evident. Indeed, a third of gastrinoma patients have troublesome diarrhoea, and this feature is also seem in the glucagonoma syndromedespite normal v.i.p. and in many cases normal pancreatic polypeptide (P.P.) levels.6 It is possible that P.P. may be associated with diarrhoea, though many patients with high plasma-p.p. values (e.g., with insulinomas) have no diarrhoea.6 We are studying a patient with diarrhoea, normal v.i.p., and high plasma-p.p. produced by hepatic metastases of a pancreatic P.P.-oma, and it is indeed possible that P.P. is responsible for the clinical symptoms. That v.i.p. is responsible for diarrhoea of v.i.p.-omas is incontrovertible. Infusions of v.i.p. in pigs producing similar blood levels result in severe diarrhcea.7 A third of pancreatic v.i.p.-omas
MACROPHAGES v. CANCER
most
with massive diarrhoea have absent tumour P.P. cells and normal plasma P.P. levels.6 Ganglioneuromas producing v.i.p. and 9 watery diarrhoea* are never associated with excess P.P. production. Departments of Histochemistry and Medicine, Royal Postgraduate Medical School, London W12
melanoma’ and with cancer of the prostate,2have emphasised the importance of macrophages in this form of immunotherapy. B.C.G. contact suppression of tumours is a hostmediated response since the organisms are not directly cyto-
cutaneous
toxic for
tumour
cells, but
treatment
is successful in animals
lacking full lymphocyte competence. Thus, B.C.G. contact therapy of syngeneically transplanted rat tumours is successful even in immunosuppressed animals,3 4 and rat tumours xenografted to athymic "nude" mice may be prevented from FACILITATION OF B.C.G. CONTACT SUPPRESSION OF HEPATOMA
D23
BY
SYNGENEIC MACROPHAGES
S. R. BLOOM A. G. EVERSON PEARSE
Strip. In Gaza asthma is an extremely common disease among both children and adults. While no exact figures exist concerning its incidence in the population, it is among the most frequent diagnoses made in the outpatient clinics and emergency room of our hospital, with a frequency reaching 10—20% of all children examined. In contrast with Godfrey’s findings, no significant difference in the incidence of the disease could be seen among children from city, village, or refugee camps. If any difM. G., Bloom, S. R., Polak, J. M., Albyquerque, R. H., Modlin, I., Pearse, A G. E. Lancet, 1976, i, 991. 2 Said, S I., Rosenberg, R. N. Science, 1976, 192, 907. 3. Polak, J. M., Pearse, A. G. E., Garaud, J.-C., Bloom, S. R. Gut, 1974, 15,
Bryant,
720. 4. Bloom, S
SIR,-Your editorial (July 3, p. 27) draws attention to the paucity of knowledge concerning the role of macrophages both in immunosurveillance and in immunotherapy of cancer. Recent results, from this and other laboratories, of investigations on the mechanism of action ofB.c.G. regionally applied to tumour deposits, such as has been well described clinically with
J. M. POLAK
IgE, PARASITES, AND ALLERGY SIR,—Iwas astonished to realise that a generalisation such as the one which appears in your editorial of April 24 (p. 894}-"there is evidence for an inverse relation between parasites and allergy: asthma and hay fever are rare in parts of the world where the population is heavily parasitised"-was based uniquely on the findings of Godfrey in the Gambia.’° While this may be true in the Gambia, it certainly is not in the Gaza
1.
E. E. LASCH
subsequently by Said and Rosenberg.2 However, not only a neural peptide, for numerous endocrine
and
R., Polak, J. M. in Gastrointestinal Hormones (edited by J. C. Thompson),p. 635. Austin, Texas, 1975. 5. Mallinson, C. M., Bloom, S. R., Warin, A. P., Salmon, P. R., Cox, B. Lancet, 1974, ii, 1. 6 Polak. J M , Bloom, S. R., Adrian, T. E., Heitz, Ph., Bryant, M. G., Pearse, A G. E. ibid. 1976, i, 328. 7 Bloom. S R., Mitchell, S. J., Modlin, I. (Unpublished). 8 Swift, P. G. F., Bloom, S. R., Harris, F. Archs Dis. Childh. 1975, 50, 896. 9 Bloom, S. R., Polak, J. M., Pearse, A. G. E. Lancet, 1973, ii, 14. 10 Godfrey. R C Clin. Allergy, 1975, 5, 201.
*Glaxo percutaneous
vaccine B.P., 3x10’ viable units/mg organisms, representing approximately 20% viability.
moist
weight
of
type of B.C.G. therapy.’ In contrast, treatment of animals with particulate silica, of a type known to be selectively toxic for macrophages, abrogates B.C.G.-mediated tumour contact suppression both in rats6 and athymic mice,6 indicating that macrophages play a primary and important role in this type of local therapy. Furthermore, whilst transplanted rat tumours normally contain a proportion of host macrophages, varying widely between tumour types, there is a distinct correlation between the maximum number of cells of each tumour that can be suppressed by contact with B.C.G. and the extent of its host macrophage infiltration.8 Thus, tumours containing 25-30% macrophages (e.g., chemically induced sarcomas) are highly susceptible to B.c.G. therapy, whereas those containing only 2-3% macrophages (e.g., mammary carcinomas) are less responsive. Most importantly, our findings
growth by this
1.
D. L., Eilber, F. R., Holmes, E. C., Cancer Immun. Immunother. 1976, 1, 93.
Morton,
Sparks,
F.
C., Ramming, K. P.
Merrin, C., Han, T, Klein, E., Wajsman, Z., Murphy, G. P Cancer Chemother. Rep. 1975, 59, 157. 3 Pimm, M. V., Baldwin, R. W Br J. Cancer (in the press). 4. Moore, M, Lawrence, N., Nisbet, N. W. Int. J Cancer, 1975, 15, 891. 5 Pimm, M. V, Baldwin, R. W. Nature, 1975, 254, 77. 6. Hopper, D. G, Pimm, M. V., Baldwin, R. W. Cancer Immun. Immunother. 1976, 1, 143. Chassoux, D., Salomon, J.-C Int J. Cancer, 1975, 16, 515. 8 Baldwin, R. W. Transplant. Rev. 1976, 28, 62.
2
7
