02373nas a2200349   4500000000100000008004100001260001300042653002700055653001200082653002500094653004400119653001100163653003100174653002100205653002100226653001900247653001800266653001500284653000900299653002200308653000900330653002000339653001400359100001200373700001800385700001800403245008100421300001100502490000800513520148800521022001402009       2000                            d  c2000 Jun10aAdjuvants, Immunologic10aAnimals10aAntinematodal Agents10aDose-Response Relationship, Immunologic10aFemale10aGene Expression Regulation10aImmunoglobulin E10aInterferon-gamma10aInterleukin-1810aInterleukin-410aLevamisole10aMale10aMercuric Chloride10aRats10aRats, Inbred BN10aTh2 Cells1 aSzeto C1 aGillespie K M1 aMathieson P W00aLevamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance.  a217-240 v1003 a<p>Immune responses can be classified, according to the predominant cytokines involved, into type 1 (featuring interferon-gamma, IFN-gamma) and type 2 (featuring interleukin-4, IL-4); imbalance between type 1 and type 2 cytokine compartments has been implicated in many human diseases. Levamisole is a drug with an unknown mode of action that has been used to boost immunity in infectious diseases including leprosy, and in some cancers. To test the hypothesis that levamisole acts by inducing a shift to a type 1 immune response, we used Brown Norway (BN) rats, which are markedly biased to type 2 responses. BN rats treated with levamisole showed a dose-dependent rise in serum IFN-gamma and fall in serum immunoglobulin E (IgE) level. Detailed analysis of cytokine gene expression showed upregulation of IFN-gamma and downregulation of IL-4 messenger RNA. This coincided with marked upregulation of IL-18, a recently characterized cytokine with potent activity in stimulating IFN-gamma production. IL-12 was not induced. Further, the type 2 response induced in BN rats by mercuric chloride was markedly attenuated when rats were pretreated with levamisole: there was a 2-log reduction in maximum serum IgE level and marked attenuation of IL-4 gene upregulation. These data indicate that levamisole acts by resetting the immune balance towards a type 1 response via induction of IL-18. Our findings provide a direction for development of more specific immunomodulating therapy.</p>  a0019-2805