Local pathological responses to slow-release recombinant interleukin-1, interleukin-2 and gamma-interferon in the mouse and their relevance to chronic inflammatory disease.

1. The present study describes the pathological responses to local administration of recombinant cytokines in subcutaneously implanted slow-release ethylene vinyl acetate (EVA) co-polymer in mice. 2. EVA-recombinant human interleukin-1 beta (10(4) units) implants induced the formation of chronic granulomatous inflammatory tissue between 4 and 7 days after implantation, characterized by predominant macrophage infiltration, neovascularization and fibrosis which persisted up to 21 days after-implantation. EVA-recombinant human interleukin-1 alpha (10(4)-10(5) units) implants induced a qualitatively similar but less intense response. 3. In contrast, recombinant human interleukin-2 (10(2)-10(4) units) implants resulted in early lymphocytic vasculitis (4 days) and the development of a predominantly lymphoid lesion comprised of lymphoblasts and significant mononuclear cell proliferation by 7 days. 4. EVA-recombinant gamma-interferon (10(3)-10(4) units) implants failed to elicit a significant tissue response; with the exception of multinucleate giant cell formation the characteristics of these lesions closely resembled the mild fibrotic responses observed for EVA-bovine serum albumin (0.5-12.5 mg) implants. 5. These observations suggest that continuous endogenous local release of interleukin-1 or interleukin-2 in vivo is sufficient for the development of specific pathological features characterizing chronic immuno-inflammatory diseases.