Interleukin-12 (IL-12)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

IL-12 family cytokines are immunological playmakers that mediate surprisingly diverse functional effects (Nature, 2012 http://buff.ly/PE2xeG).

Source: Macrophages, dendritic cells

Crystal structure of human IL-12, Wikipedia, public domain.

IL-12 effects

- T cells: TH1 differentiation
- NK cells and T cells: IFN-γ synthesis, increased cytotoxic activity

IL-12 is the main cytokine that activates STAT4.

IL-12 consists of two subunits - p35 and p40.

IL-12 binds to a type I receptor, composed of β1 and β2 subunits:

- p35 binds to β2 receptor, leading to Jak 2 activation and STAT4

- p40 binds to β1 receptor, leading toTyk 2 activation and STAT4

IL-12 sends a powerful signal to naive T cells, directing their differentiation to TH, shifting immune response towards cell-mediated immunity. In asthma, production of IL-12 by blood cells and expression in airway is impaired.

IL-18 is synergistic with IL-12.

Trials

Injection of rh IL-12 reduces circulating eosinophils in asthma. Treatment was not well tolerated: flu-like symptoms, abnormal LFTs and arrhythmias. Not actively developed as a therapy.

References

Bryan, SA, O'Connor, BJ, Matti, S, et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356:2149.

Related reading

IL-12 in Wikipedia.

Ustekinumab is a Strong Option for Moderate to Severe Psoriasis - anti-IL12/23 monoclonal antibody with NNT of 2 http://goo.gl/gbXSJ

Published: 04/09/2010
Updated: 08/09/2011