, Volume 7, Issue 3, pp 227–232 | Cite as

Abnormal regulation of inflammatory skin responses in male patients with chronic granulomatous disease

  • John I. Gallin
  • E. Stephen Buescher
Original Article


A common characteristic of the response to infection seen in patients with chronic granulomatous disease (CGD) is an exaggerated and prolonged inflammatory response with frequent development of draining lymph nodes and granuloma formation. Recent reports of several CGD patients with minor but significant in vitro abnormalities of cellular and humoral components of neutrophil chemotactic responses would predict lessened responses to inflammatory stimuli. The following studies were, therefore, performed to assess in vivo inflammatory responses in patients with CGD. Twenty-four-hour Rebuck skin-window procedures were performed on eight patients (five male and three female) with CGD and on ten volunteers. The windows were changed 1, 3, 5,8, 12, and 24 h after the abrasion. Quantitation of the skin windows was performed with the assistance of a microscopeimage analyzer computer facility. Neutrophil accumulation into skin windows was normal in CGD patients throughout the first 5 h. However, during the 8-to 24-h period, when neutrophils characteristically disappear from normal inflammatory responses and are replaced by monocytes, there was abnormal persistence of PMN at the inflammatory foci in male but not in female CGD patients (P< 0.05 for the comparison of the rates of decline of PMN, from hour 8 to hour 24, in five male CGDs and in 10 normals). Monocyte recruitment was normal. In one CGD male, the abnormal skin-window response was normalized while he was receiving white cell transfusions. The data indicate that there is an abnormal “turn off” of the acute inflammatory response in male CGD patients and support a modulatory role for products of oxidative metabolism on the inflammatory response. In addition, they indicate that the mild in vitro defect in neutrophil chemotaxis is not associated with a depressed, acute inflammatory response in vivo and, therefore, does not explain the increased susceptibility of CGD patients to certain infections.


Chronic Granulomatous Disease Drain Lymph Node Granuloma Formation Inflammatory Skin Acute Inflammatory Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Johnston, R. B., andS. L. Newman. 1977. Chronic granulomatous disease.Pediatr. Clin. North Am. 24(2):365–376.Google Scholar
  2. 2.
    Klebanoff, S. J. 1982. Oxygen-depedent cytotoxic mechanisms of phagocytes.In Advances in Host Defense Mechanisms, Vol. 1, Phagocytic Cells. J. I. Gallin and A. S. Fauci, editors. Raven Press, New York, 111–162.Google Scholar
  3. 3.
    Mills, E. L., andP. G. Quie. 1980. Congenital disorders of the functions of polymorphonuclear neutrophils.Rev. Infect. Dis. 2:205–517.Google Scholar
  4. 4.
    Seligmann, B. E., andJ. I. Gallin. 1980. Use of lipophilic probes of membrane potential to assess human neutrophil activation. Abnormality in chronic granulomatous disease.J. Clin. Invest. 66:493–503.Google Scholar
  5. 5.
    Whiten, J. C., C. E. Chapman, E. R. Simons, M. E. Chovaneic, andH. J. Cohen. 1980. Correlation between membrane potential changes and Superoxide production in human granulocytes stimulated by phorbol myristate acetate: Evidence for defective activation in chronic granulomatous disease.J. Biol. Chem. 255:1874–1878.Google Scholar
  6. 6.
    Lew, P. D., F. S. Southwick, T. P. Stossel, J. C. Whitin, E. Simons, andH. J. Cohen. 1981. A variant of chronic granulomatous disease: Deficient oxidative metabolism due to a lowaffinity NADPH oxidase.N. Engl. J. Med. 305:1329–1333.Google Scholar
  7. 7.
    Gallin, J. I., M. P. Fletcher, B. E. Seligmann, S. Hoffstein, K. Cehrs, andN. Mounessa. 1982. Human neutrophil-specific granule deficiency: A model to assess the role of neutrophilspecific granules in the evolution of the inflammatory response.Blood 1982:1317–1329.Google Scholar
  8. 8.
    Rebuck, J. W., andJ. H. Crowley. 1955. A method of studying leukocyte function in vivo.Ann. NY Acad. Sci. 57:757–805.Google Scholar
  9. 9.
    Buescher, E. S., andJ. I. Gallin. 1982. Leukocyte transfusions in chronic granulomatous disease. Persistence of transfused leukocytes in sputum.New Eng. J. Med. 307:800–803, 1982.Google Scholar
  10. 10.
    Dale, D. C., andS. M. Wolff. 1971. Skin window studies of the acute inflammatory responses of neutropenic patients.Blood 38:138–142.Google Scholar
  11. 11.
    Clark, R. A., andS. J. Klebanoff, 1978. Chronic granulomatous disease. Studies of a family with impaired neutrophil chemotactic, metabolic and bactericidal function.Am. J. Med. 65:941–948.Google Scholar
  12. 12.
    Mills, E. L., K. S. Rholl, andP. G. Quie. 1980. X-linked inheritance infernales with chronic granulomatous disease.J. Clin. Invest. 66:332–340.Google Scholar
  13. 13.
    Clark, R. A., andS. J. Klebanoff. 1979. Chemotactic factor inactivation by the myeloperoxidase-hydrogen peroxide-halide system.J. Clin. Invest. 64:913–920.Google Scholar
  14. 14.
    Clark, R. A., S. Szot, K. Venkatasubramanian, andE. Schiffmann. 1980. Chemotactic factor inactivation by myeloperoxidase-mediated oxidation of methionine.J. Immunol. 124: 2020–2026.Google Scholar
  15. 15.
    Tsan, M., andR. C. Denison. 1981. Oxidation of n-formyl methionyl chemotactic peptide by human neutrophils.J. Immunol. 126:1387–1389.Google Scholar
  16. 16.
    Voetman, A. A., R. S. Weening, M. N. Hamers, L. F. Meerhof, Annet A. A. M. Bot, andD. Roos. 1981. Phagocytosing human neutrophils inactivate their own granular enzymes.J. Clin. Invest. 67:1541–1549.Google Scholar
  17. 17.
    Wright, D. G., andJ. I. Gallin. 1975. Modulation of the inflammatory response by products released from human polymorphonuclear leukocytes during phagocytosis: Generation and inactivation of the chemotactic factor C5a.Inflammation 1:23–39.Google Scholar
  18. 18.
    Wright, D. G., andJ. I. Gallin. 1977. A functional differentiation of human neutrophil granules: Generation of C5a by a specific (secondary) granule product and inactivation of C5a by azurophil (primary) granule products.J. Immunol. 119:1068–1076.Google Scholar
  19. 19.
    Venge, P., andI. Olsson. 1975. Cationic proteins of human granulocytes VI. Effects on the complement system and mediation of chemotactic activity.J. Immunol 115:1505–1508.Google Scholar
  20. 20.
    Roos, D., R. S. Weening, S. R. Wyss, andE. A. Hugo. 1980. Protection of human neutrophils by endogenous catalase. Studies with cells from catalase-deficient individuals.J. Clin. Invest. 65:1515–1522.Google Scholar

Copyright information

© Plenum Publishing Corporation 1983

Authors and Affiliations

  • John I. Gallin
    • 1
    • 2
  • E. Stephen Buescher
    • 1
  1. 1.Bacterial Diseases SectionLaboratory of Clinical Investigation National Institute of Allergy and Infectious DiseasesBethesda
  2. 2.Bacterial Diseases SectionNational Institutes of HealthBethesda

Personalised recommendations