Immune complex-induced lung and dermal vascular injury. Differing requirements for tumor necrosis factor-alpha and IL-1.

Abstract

Vascular injury has been induced in rat lung and dermis after deposition of IgG immune complexes (BSA-anti-BSA complexes). By the use of antibodies to TNF-alpha and IL-1 and employment of the IL-1R antagonist, the requirements for these cytokines have been evaluated. In lung, both TNF-alpha and IL-1 were required for the full expression of injury. Protection was related to the dose of cytokine-blocking agent employed and was directly correlated with diminished tissue content of myeloperoxidase (MPO). In the dermis, IL-1 was required for the full expression of injury; blocking of IL-1 protected the tissue from injury in a manner that correlated with reduced MPO content. However, anti-TNF-alpha provided no protection against dermal vascular injury and failed to reduce MPO content. In contrast, the local injection of either TNF-alpha or IL-1 beta enhanced IgG immune complex-induced dermal vascular injury, proportional to the increased tissue content of MPO, indicating that the rat dermis is reactive to both cytokines. By the employment of immunohistochemical approaches, it was demonstrated that, after deposition of immune complexes, TNF-alpha and IL-1 were readily demonstrated in lung macrophages, whereas in the dermis IL-1, but not TNF-alpha, was present in a granular pattern within interstitial cells. The immunohistochemical data are consistent with the patterns of protective effects of anti-IL-1, IL-1R antagonist and anti-TNF-alpha in the two organs. As expected, blocking of TNF-alpha or IL-1 had no protective effects on acute lung injury produced by systemic C activation after i.v. infusion of the cobra venom factor. The data suggest fundamental differences in the requirements for cytokines in lung and dermal vascular injury after deposition of IgG immune complexes.

• Authors: M S Mulligan, P A Ward
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 149 Issue 1 Pg. 331-9 (Jul 01 1992) ISSN: 0022-1767 [Print] United States
• PMID: 1318904 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigen-Antibody Complex
• Interleukin-1
• Receptors, Immunologic
• Receptors, Interleukin-1
• Tumor Necrosis Factor-alpha
• Peroxidase

Topics

• Alveolitis, Extrinsic Allergic (immunology, pathology)
• Animals
• Antigen-Antibody Complex (immunology)
• Capillary Permeability
• Immune Complex Diseases (immunology)
• Interleukin-1 (immunology)
• Neutrophils (immunology)
• Peroxidase (metabolism)
• Rats
• Receptors, Immunologic (physiology)
• Receptors, Interleukin-1
• Tumor Necrosis Factor-alpha (immunology)
• Vasculitis, Leukocytoclastic, Cutaneous (immunology, pathology)