Mouse interleukin-36 beta [IL-36B; previously IL-1F8, FIL-1H (eta) and IL-1H2] is a member of the IL-1 family of proteins that includes IL-1B, IL-1A, IL-1ra, IL-18, IL-36Ra/IL-1F5, IL-36A/IL-1F6, IL-37/IL-1F7, IL-36G/IL-1F9 and IL-1F10. All family members show a 12 B-stranded B-trefoil configuration, share up to 50% aa sequence identity, and are believed to have arisen from a common ancestral gene. Although two alternatively spliced transcript variants for human IL-36B/IL-1F8 have been described, to date, only one mouse IL-36B/IL-1F8 isoform is known. Mouse IL-36B/IL-1F8 is synthesized as a 183aa protein that contains no signal sequence, no prosegment and no potential N-linked glycosylation site(s). Mouse IL-36B/IL-1F8 shares 61% and 74% aa identity with human IL-36B isoform 2 and rat IL-36B, respectively. IL-36B is agonistic, stimulating release of inflammatory mediators such as IL-6 and IL-8, and cytotoxic peptides such as beta-defensins 2 and 3 that aid in defense against microbial pathogens. The receptor for IL-36 proteins is IL-1 Rrp2, with IL-1 RAcP as a coreceptor. Antagonism of IL-36 proteins by IL-36Ra, which also binds IL-1 Rrp2, has been shown by some investigators. Skin keratinocytes express highest levels of IL-36 proteins and their receptors, followed by epithelia in the esophagus, trachea and bronchae. IL-36B expression is increased in psoriatic skin and may play a role in pathogenesis of psoriasis. IL-36B is also expressed in resting and activated monocytes and B cells, synovial fibroblasts, neurons and glia, and is detectable in plasma and body fluids. IL-36B, along with IL-36A and IL-3G, is up-regulated by IL-A and TNF-A in keratinocytes, and has been shown to activate NF-kB and MAPK signaling pathways in an IL-1 Rrp2-dependent manner. Full-length recombinant IL-36 proteins appear less active than their endogenous counterparts, but trimming of the N-termini enhances their activity.