Acute and chronic inflammatory responses to local administration of recombinant IL-1 alpha, IL-beta, TNF alpha, IL-2 and Ifn gamma in mice.
The contention that cytokines are important mediators of inflammation prompted the present studies which were designed to compare acute and chronic pathological effects of locally-administered recombinant (r) IL-1 alpha, IL-1 beta, TNF alpha, IL-2 and Ifn gamma. Acute (6 hr), resolving (48 hr) inflammation was induced by the following, in order of potency: rIL-1 alpha greater than rIL-1 beta greater than rTNF alpha greater than rIfn gamma = BSA (control) following a single sc. injection. However, only rIL-1 beta and rIL-2 initiated and maintained chronic granulomatous reactions when delivered locally from a sc. ethylene vinyl acetate (EVA) slow-release polymer. The predominance of macrophages in EVA-rIL-1 beta lesions contrasted with the proliferative lymphoid granulomata induced by EVA-rIL-2 implants. These "in vivo" observations reinforce the roles of both IL-1 beta and IL-2 as potent mediators of chronic immunoinflammatory disease.
Dunn
C J
CJ
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 94001.
Hardee
M M
MM
Staite
N D
ND
D000818:Animals; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000633:toxicity*; D007375:Interleukin-1 / Q000633:toxicity*; D007376:Interleukin-2 / Q000633:toxicity*; D051379:Mice; D011994:Recombinant Proteins / Q000633:toxicity; D012867:Skin / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma