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.
Dunn
C J
CJ
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Hardee
M M
MM
Gibbons
A J
AJ
Staite
N D
ND
Richard
K A
KA
D000818:Animals; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D005260:Female; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D003692:Delayed-Action Preparations; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma