Allergen-induced depression neutrophil chemotaxis in allergic individuals
of
Jerry
R. Hill* Salt Luke City, Utah
L. Rubin,
Robert
W. Griffiths,
and Harry
In previous studies we have shown that neutrophil (PMN) chemotaxis is depressed in patients with allergic disease, hyperimmunoglobulinemia E, and recurrent infections. Although a number of these patients have now been described, little is known about the mechanism of defective PMN ,function in such individuals. The present studies were carried out to de$ne the relationship between defective PMN chemotaxis and allergic hypersensitivity. Neutrophil chemotaxis was assessed in individuals with sensitivity to ragweed pollen as documented by intradermal skin testing. In each patient, chemotaxis was measured before and after in vitro exposure of their leukocytes to ragweed. A total of 21 individuals in 3 groups have been studied. These include 7 patients with allergic symptomatology and recurrent infections who were ragweed sensitive, 6 patients with a prior history of ragweed sensitivity who had undergone successful desensitization, and 8 nonatopic control subjects. Following in vitro exposure of the leukocytes qf the 7 symptomatic patients to ragweed, a profound depression (5470 -t 16Yo) in chemotatic activity was noted. In contrast the control subjects and 6 desensitized patients showed no depression of PMN chemotaxis. Further studies were carried out which demonstrate the antigen-specific nature of the phenomenon and the ability to transfer the depression to normal cells suspended in allergic serum. These data suggest that defective PMN chemotaxis in allergic patients results from an interaction, either directly or indirectly, of antigen with sensitized leukocytes. Specific immunotherapy may have an effect to prevent the chemotactic abnormality in these patients.
The initial inflammatory responseto invasion of the body by pathogenic microorganismsis critical as a determinant of the outcome of infection. Animal studies have demonstratedthat a critical 2- to 4-hr period exists after bacterial invasion during which an intact inflammatory responsemust be presentif infection is to be prevented or suppressed.‘*2 In previous studies we have demonstrated that the circulating
neutrophils of otherwise normal patients with cutaneous,3 pulmonary,4 and systemic bacterial infections5are hyperactive in their responseto chemotactic stimulation and have suggestedthat this may be an important mechanismin localizing or preventing clinical infection. More recently we have described a number of patients with marked allergic diseasesincluding eczema,6-s urticaria,1° and allergic rhinitis” who have a profound defect in neutrophil granulocyte chemotaxis. Each of thesepatientshassuffered severe or recurrent infections most commonly associated with exacerbationsof their allergic disease.” In addition to these severely affected patients, we believe there is an additional population of allergic individuals who may only have mild respiratory infections such assinusitis, bronchitis, and otitis media or those who have superficial abscessdisease. While it is generally felt that such complications are due to the edema and congestion associatedwith the allergic reaction, it is conceivable that mediators of this responsemay also affect the local or even systemic inflammatory reaction. This could conceivably contribute to the infections suffered by such individuals.
From the Division of Clinical Immunology, Departments of Pediatric!; and Medicine, and the Department of Pathology, University 01‘ Utah. Supported in part by United States Public Health Service Grants AM1835,4, AM21140, and A113150 and a grant from the Thrasher Foundation. Presented in part at the meetings of the Society for Pediatric Research, San Francisco, April 30, 1977. Received for publication Nov. 14, 1977. Accepted for publication July 24, 1978. Reprint requests to: Harry R. Hill, Division of Clinical Immunology and Allergy, University of Utah Medical Center, Salt Lake City, UT 84132. *Dr. Hill is an Investigator of the Howard Hughes Medical Institute 0091-674978/110301+08$00.80/0
0 1978 The
C. V. Mosby
Co.
Vol.
62, No.
5 pp. 301-308
302
TABLE
Rubin, Griffiths, and Hill I. Clinical
data from
J. ALLERGY
symptomatic
patients
with
allergic
Age Patient-
(v)
1, D. K.
24
2, M. M.
30
3, J. S.
40
4, B. R. 5, J. S.
35 14
6, H. S.
27
7, J. M. Control subjects
34
Allergic rhinitis, sinusitis, recurrent respiratory infection Allergic rhinitis, sinusitis, recurrent respiratory infection Allergic rhinitis, skin abscesses, pneumonia Asthma, pneumonia, abscesses Eczema, abscesses, allergic rhinitis, pneumonia, sinusitis, otitis, diarrhea Allergic rhinitis, asthma, abscesses, recurrent respiratory infection Allergic rhinitis, sinusitis
MATERIALS AND METHODS Clinical material A total of 21 individuals were studied. Eight of these were nonatopic individuals without a history of allergic disease or recurrent infections who served as normal control subjects. Seven of the 21 had marked allergic symptomatology and a history of severe or recurrent infections including sinusitis, otitis, bronchitis, pneumonia, and cutaneous abscesses (Table I). Patient D. K. has chronic sinusitis which usually yielded S. aureus on nasopharyngeal culture. He had undergone multiple courses of antibiotics which helped temporarily, but this was immediately followed by the reappearance of symptomatic sinusitis. Patient M. M. is a 30-yr-old laboratory worker with a marked history of allergic rhinitis who also suffers chronic sinusitis which is extremely resistant to antibiotic therapy. She claims to have an unusual incidence of viral respiratory infections which seem to persist for an extended period of time (
of
Jerry
R. Hill* Salt Luke City, Utah
L. Rubin,
Robert
W. Griffiths,
and Harry
In previous studies we have shown that neutrophil (PMN) chemotaxis is depressed in patients with allergic disease, hyperimmunoglobulinemia E, and recurrent infections. Although a number of these patients have now been described, little is known about the mechanism of defective PMN ,function in such individuals. The present studies were carried out to de$ne the relationship between defective PMN chemotaxis and allergic hypersensitivity. Neutrophil chemotaxis was assessed in individuals with sensitivity to ragweed pollen as documented by intradermal skin testing. In each patient, chemotaxis was measured before and after in vitro exposure of their leukocytes to ragweed. A total of 21 individuals in 3 groups have been studied. These include 7 patients with allergic symptomatology and recurrent infections who were ragweed sensitive, 6 patients with a prior history of ragweed sensitivity who had undergone successful desensitization, and 8 nonatopic control subjects. Following in vitro exposure of the leukocytes qf the 7 symptomatic patients to ragweed, a profound depression (5470 -t 16Yo) in chemotatic activity was noted. In contrast the control subjects and 6 desensitized patients showed no depression of PMN chemotaxis. Further studies were carried out which demonstrate the antigen-specific nature of the phenomenon and the ability to transfer the depression to normal cells suspended in allergic serum. These data suggest that defective PMN chemotaxis in allergic patients results from an interaction, either directly or indirectly, of antigen with sensitized leukocytes. Specific immunotherapy may have an effect to prevent the chemotactic abnormality in these patients.
The initial inflammatory responseto invasion of the body by pathogenic microorganismsis critical as a determinant of the outcome of infection. Animal studies have demonstratedthat a critical 2- to 4-hr period exists after bacterial invasion during which an intact inflammatory responsemust be presentif infection is to be prevented or suppressed.‘*2 In previous studies we have demonstrated that the circulating
neutrophils of otherwise normal patients with cutaneous,3 pulmonary,4 and systemic bacterial infections5are hyperactive in their responseto chemotactic stimulation and have suggestedthat this may be an important mechanismin localizing or preventing clinical infection. More recently we have described a number of patients with marked allergic diseasesincluding eczema,6-s urticaria,1° and allergic rhinitis” who have a profound defect in neutrophil granulocyte chemotaxis. Each of thesepatientshassuffered severe or recurrent infections most commonly associated with exacerbationsof their allergic disease.” In addition to these severely affected patients, we believe there is an additional population of allergic individuals who may only have mild respiratory infections such assinusitis, bronchitis, and otitis media or those who have superficial abscessdisease. While it is generally felt that such complications are due to the edema and congestion associatedwith the allergic reaction, it is conceivable that mediators of this responsemay also affect the local or even systemic inflammatory reaction. This could conceivably contribute to the infections suffered by such individuals.
From the Division of Clinical Immunology, Departments of Pediatric!; and Medicine, and the Department of Pathology, University 01‘ Utah. Supported in part by United States Public Health Service Grants AM1835,4, AM21140, and A113150 and a grant from the Thrasher Foundation. Presented in part at the meetings of the Society for Pediatric Research, San Francisco, April 30, 1977. Received for publication Nov. 14, 1977. Accepted for publication July 24, 1978. Reprint requests to: Harry R. Hill, Division of Clinical Immunology and Allergy, University of Utah Medical Center, Salt Lake City, UT 84132. *Dr. Hill is an Investigator of the Howard Hughes Medical Institute 0091-674978/110301+08$00.80/0
0 1978 The
C. V. Mosby
Co.
Vol.
62, No.
5 pp. 301-308
302
TABLE
Rubin, Griffiths, and Hill I. Clinical
data from
J. ALLERGY
symptomatic
patients
with
allergic
Age Patient-
(v)
1, D. K.
24
2, M. M.
30
3, J. S.
40
4, B. R. 5, J. S.
35 14
6, H. S.
27
7, J. M. Control subjects
34
Allergic rhinitis, sinusitis, recurrent respiratory infection Allergic rhinitis, sinusitis, recurrent respiratory infection Allergic rhinitis, skin abscesses, pneumonia Asthma, pneumonia, abscesses Eczema, abscesses, allergic rhinitis, pneumonia, sinusitis, otitis, diarrhea Allergic rhinitis, asthma, abscesses, recurrent respiratory infection Allergic rhinitis, sinusitis
MATERIALS AND METHODS Clinical material A total of 21 individuals were studied. Eight of these were nonatopic individuals without a history of allergic disease or recurrent infections who served as normal control subjects. Seven of the 21 had marked allergic symptomatology and a history of severe or recurrent infections including sinusitis, otitis, bronchitis, pneumonia, and cutaneous abscesses (Table I). Patient D. K. has chronic sinusitis which usually yielded S. aureus on nasopharyngeal culture. He had undergone multiple courses of antibiotics which helped temporarily, but this was immediately followed by the reappearance of symptomatic sinusitis. Patient M. M. is a 30-yr-old laboratory worker with a marked history of allergic rhinitis who also suffers chronic sinusitis which is extremely resistant to antibiotic therapy. She claims to have an unusual incidence of viral respiratory infections which seem to persist for an extended period of time (
