A Humanized Monoclonal Antibody against Heat Shock Protein 60 Suppresses Murine Arthritis and Colitis and Skews the Cytokine Balance toward an Anti-Inflammatory Response

• Published in: The Journal of immunology (1950) 2015-06, Vol.194 (11), p.5103-5109
• Main Authors: Ulmansky, Rina, Landstein, Dorit, Moallem, Eli, Loeb, Virginie, Levin, Avi, Meyuhas, Ronit, Katzavian, Galia, Yair, Shira, Naparstek, Yaakov
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Arthritis, Experimental - drug therapy; Bacterial Proteins - immunology; Cell Line, Tumor; Chaperonin 60 - antagonists & inhibitors; Chaperonin 60 - immunology; Female; Humans; Inflammatory Bowel Diseases - drug therapy; Interferon-gamma - secretion; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-10 - secretion; Interleukin-6 - secretion; Jurkat Cells; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mycobacterium tuberculosis; Protein Binding - immunology; Rats; Rats, Inbred Lew
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500023

We have previously shown that naturally occurring as well as acquired Abs against the Mycobacterium tuberculosis heat shock protein (HSP)65 protect against the induction of murine autoimmune inflammatory arthritis. In the present work, we have studied the anti-inflammatory effect of prozumab, a humanized anti-HSP mAb in murine inflammatory arthritis and colitis, and its effects on cytokine secretion. Prozumab was shown to bind to HSP60, the highly conserved mammalian homolog of the bacterial protein, and it was found to be effective in protecting and suppressing autoimmune arthritis in the models of adjuvant arthritis and collagen-induced arthritis in rats and mice, respectively, as well as in acute hapten-mediated colitis and chronic, spontaneous colitis models. Mechanistically, prozumab induces IL-10 secretion from naive human PBMCs and suppresses the secretion of IFN-γ and IL-6 from anti-CD3-activated human PBMCs. These findings make prozumab a promising potential drug for treating human rheumatoid arthritis and inflammatory bowel disease, as well as a wide range of autoimmune inflammatory diseases.