Failure of IL-1 receptor antagonist and monoclonal anti-IL-1 receptor antibody to inhibit antigen-specific immune responses in vivo

• Published in: The Journal of immunology (1950) Vol. 148; no. 3; pp. 766 - 771
• Main Authors: Faherty, DA, Claudy, V, Plocinski, JM, Kaffka, K, Kilian, P, Thompson, RC, Benjamin, WR
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.02.1992; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antibodies, Monoclonal; Antibody Formation - drug effects; Antigens - immunology; Biological and medical sciences; Cells, Cultured; Cytotoxicity, Immunologic - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; In Vitro Techniques; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - pharmacology; Interleukin-6 - biosynthesis; Lymphokines, interleukins ( function, expression); Mice; Mice, Inbred C57BL; Proteins - pharmacology; Receptors, Immunologic - physiology; Receptors, Interleukin-1; Regulatory factors and their cellular receptors; Sialoglycoproteins; T-Lymphocytes, Cytotoxic - immunology; Biological properties; Immune response; Rodentia; Cytokine; Cellular immunity; Monoclonal antibody; In vivo; Vertebrata; Mammalia; Mouse; Interleukin 1; Antagonist; Humoral immunity; Biological receptor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.148.3.766

rIL-1R antagonist (rIL-1ra) and 35F5, a neutralizing mAb, have been shown to inhibit the ability of IL-1 alpha and IL-1 beta to bind to type I but not type II murine receptors. Additionally, IL-1ra and 35F5 inhibit a variety of inflammatory responses in vitro and in vivo. In the present report we have evaluated the activity of human IL-1ra and 35F5 in murine Ag-specific cell-mediated and humoral immune response models. Administration of IL-1ra, either twice daily or as a continuous infusion, did not inhibit the cytolytic T lymphocyte response to allogeneic splenocytes. The CTL response was also not inhibited by daily administration of 35F5. The delayed type hypersensitivity response to oxazolone was similarly refractory to administration of IL-1ra and 35F5. In the humoral immune response models, neither the splenic plaque response to SRBC nor the IgG or IgM response to TNP-keyhole limpet hemocyanin was inhibited by treatment with IL-1ra or 35F5. These data suggest that signaling through the type I IL-1R is not required for these Ag-specific immune responses.