Interleukin-12 may increase immunologic functions in peopleinfected with HIV, according to results of an in vitro studyconducted by researchers at the National Institutes of Healthand Genetics Institute Inc.

The study, published in last week's issue of Science, wasprimarily conducted in the laboratory of lead author GeneShearer of the National Cancer Institute. Stanley Wolf ofGenetics Institute and researchers from the Lackland Air ForceBase in Texas also participated in the study.

In the study, peripheral blood mononuclear cells (PBMCs) weretaken from 40 HIV+ asymptomatic individuals and stimulatedwith the envelope (env) of HIV-1 in the presence of IL-12. TheIL-12 "appears to drive naive T helper cells to the TH1 subclassof cells" and thereby evoke a cell-mediated immune response,Dennis Harp, Genetics Institute's director of corporatecommunications explained.

Harp said the TH1 subclass of cells is associated with theproduction of IL-2 and interferon gamma, two cytokinesinvolved in cell-mediated immune response. He said IL-12 hasa proliferative effect on natural killer cells and cytolytic cells,increasing their number and stimulating them into action.These cells seek out virally infected and cancerous cells anddestroy them.

The researchers also looked at the effect of neutralizing IL-12in PBMCs from HIV- donors. They applied an IL-12 antibody tothe blood to neutralize the activity of IL-12 and then addedinfectious agents to the blood. They found that the ability ofthe PBMCs to produce IL-2 was thereby suppressed.

Shearer, et al., concluded that "the efficacy of IL-12 inaugmenting the immune function of PBMCs from HIV+ patientsraises the possibility of using IL-12 as an immune modulator toaugment the defective cell-mediated functions associated withHIV infection." They said that further studies of IL-12 in invivo models will be critical in evaluating its potential forrestoring these functions.

Genetics Institute (NASDAQ:GENIZ) of Cambridge, Mass., plansto begin clinical trials with IL-12 in the first half of 1994. Harpsaid the initial clinical study will be conducted in asymptomaticHIV-infected individuals to determine the role of IL-12 inenhancing cell-mediated immune responses. The company alsowill conduct separate trials in cancer patients.

In preclinical research conducted with Hoffmann-La Roche, IL-12 was found to suppress the growth of tumors in mice. Thatdata, by Michael Brunda, et al., was published in the Octoberissue of the Journal of Experimental Medicine. Another mousestudy conducted by researchers at the National Institute ofAllergy and Infectious Diseases indicates that IL-12 mayinduce microbial resistance in immunocompromised patients.The study was published in July in the Proceedings of theNational Academy of Sciences (see BioWorld, July 8).

The Wistar Institute in Philadelphia first discovered thebiological activity of IL-12 and in the mid-1980s began acollaboration with Genetics Institute to clone the compound.Genetics Institute acquired exclusive rights to the compound,which at that time was referred to as natural killer cellstimulatory factor (NKSF). Roche independently discovered IL-12's activity, referring to the compound as cytotoxiclymphocyte maturation factor (CLMF). The two companiessubsequently cross-licensed their patents.121393IL-12

-- Brenda Sandburg News Editor

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