Document Detail

Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key regulator of immune response and inflammation.
MedLine Citation:
PMID:  1364096     Owner:  NLM     Status:  MEDLINE    
Natural Killer cell Stimulatory Factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine of 70 kDa formed by a heavy chain of 40 kDa (p40) and a light chain of 35 kDa (p35). Although it was originally identified and purified from the supernatant of Epstein-Barr virus-transformed B cell lines, it has been shown that among peripheral blood cells NKSF/IL-12 is predominantly produced by monocytes, with lower production by B cells and other accessory cells. The most powerful inducers of NKSF/IL-12 production are bacteria, bacterial products and parasites. In addition to the biologically active p70 heterodimer, the cells producing NKSF/IL-12 also secrete a large excess of monomeric p40, a molecule with no demonstrable biological activity. NKSF/IL-12 is active on T lymphocytes and NK cells on which it induces production of lymphokines, enhancement of cytotoxic activity and mitogenic effects. NKSF/IL-12 induces T and NK cells to produce IFN-gamma and synergizes with other IFN-gamma inducers in this effect. In vitro, and probably in vivo, NKSF/IL-12 is required for optimal IFN-gamma production. When human lymphocytes are stimulated with antigens in vitro, addition of exogenous NKSF/IL-12 to the culture induces differentiation of T helper type 1 (Th1) cells, whereas neutralization of endogenous NKSF/IL-12 with antibodies favors differentiation of Th2 cells. IFN-gamma, a product of Th1 cells, enhances NKSF/IL-12 production by mononuclear cells, whereas IL-10 and IL-4, products of Th2 cells, efficiently inhibit it. Therefore, NKSF/IL-12 appears to be an important inducer of Th1 responses produced by accessory cells during early antigenic stimulation and its production is regulated by a positive feedback mechanism mediated by Th1 cells through IFN-gamma and a negative one by Th2 cells through IL-10 and IL-4. The balance of IL-12 production versus IL-10 and IL-4 production early during an immune response might therefore be instrumental in determining Th1-type versus Th2-type immune responses. Because of this potential role of IL-12 during immune responses, our results demonstrating the impaired ability of HIV seropositive patients to produce NKSF/IL-12 in response to bacterial stimulation suggest that this defect in NKSF/IL-12 production might be a factor contributing to their immune depression.
G Trinchieri; M Wysocka; A D'Andrea; M Rengaraju; M Aste-Amezaga; M Kubin; N M Valiante; J Chehimi
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Progress in growth factor research     Volume:  4     ISSN:  0955-2235     ISO Abbreviation:  Prog. Growth Factor Res.     Publication Date:  1992  
Date Detail:
Created Date:  1993-12-03     Completed Date:  1993-12-03     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8912757     Medline TA:  Prog Growth Factor Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  355-68     Citation Subset:  IM; X    
Wistar Institute, Philadelphia, PA 19104.
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MeSH Terms
Acquired Immunodeficiency Syndrome / therapy
Growth Substances / physiology*
Inflammation / immunology*
Interleukins / physiology*,  therapeutic use
Lymphocytes / physiology*
Reg. No./Substance:
0/Growth Substances; 0/Interleukins; 187348-17-0/Interleukin-12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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