The protein encoded by IL1B is a member of the interleukin 1 cytokine family. IL-1B is a potent proinflammatory cytokine and important mediator of immune responses mainly produced by monocytes and macrophages. IL-1B activates immune cells such as CD4 and CD8 T cells, upregulates expression of adhesion molecules, and induces expression of a number of other proinflammatory cytokines and other inflammation-associated proteins.
Protein expression analysis
Bone marrow cell supernatant from both wild type (WT) C57BL/6 and Heterozygous B-hIL1B mice were analyzed by ELISA.
When treated with LPS, mouse IL1B was detectable in the WT mice and heterozygous B-hIL1B mice, while human IL1B was detectable in the heterozygous B-hILIB mice, albeit being at a lower level. ND, not detectable. n=3.
Strain specific IL1B expression analysis in homozygous B-hIL1B mice by ELISA.
Bone marrow cell supernatant were collected from WT and homozygous B-hIL1B mice stimulated with LPS in vivo, and analyzed by ELISA with species-specific IL1B ELISA kit. Mouse IL1B was detectable in WT mice.Human IL1B was exclusively detectable in heterozygous B-hIL1B mice but not WT mice. ND, not detectable.
In vivo efficacy of anti human IL1B antibody
Antitumor activity of anti-human IL1B antibody in B-hIL1B mice. (A) Anti human IL1B antibody canakinumab(in house) inhibited MC38 tumor growth in B-hIL1B mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hIL1B mice (female, 6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human IL1B antibody canakinumab(in house) with different doses and schedules indicated in panel. (B) Body weight changes during treatment. As shown in panel A, anti-human IL1B antibody canakinumab(in house) was efficacious in controlling tumor growth in B-hIL1B mice, demonstrating that the B-hIL1B mice provide a powerful preclinical model for in vivo evaluation of anti-human IL1B antibodies. Values are expressed as mean ± SEM