AEGiS-11IAC: IMREG-1 and IMREG-2: two investigational immune-based therapeutics that modulate cell-mediated immunity.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

IMREG-1 and IMREG-2: two investigational immune-based therapeutics that modulate cell-mediated immunity.

Int Conf AIDS 1996 Jul 7-12; 11:221 (abstract no. Tu.A.270)
Gottlieb AA, Sizemore R, Kern C, Gottlieb M; Tulane University School of Medicine, Dept. Microbiology & Immunology, New Orleans, LA, USA. Fax:(504) 588-5144. E-mail: agottli@tmcpop.tmc.tulane.edu.

OBJECTIVE: The morbidity and mortality of HIV disease results from a complex immune dysfunctional state. Agents capable of regulating human cell-mediated immunity (CMI) represent important initiatives for therapeutic intervention. Here we determine whether a second immunomodulator, IMREG-2, recoverable from dialysable leukocyte extracts (DLE) has effects on CMI similar to those of IMREG-1. The latter has been shown to slow the course of HIV disease.

METHODS: Leukocyte dialysates have been shown to contain several modulators of immune function. Freezedried DLE from normal human donors were subjected to two-stage reverse-phase HPLC to yield IMREG-1 and chromatographically distinct IMREG-2. These subfractions were dried, frozen and reconstituted for evaluation of immunologic properties. Previously we have shown that IMREG-1 augments and accelerates human delayedtype hypersensitivity (DTH) to recall antigen in vivo, enhances the production of IFN-gamma in vitro, and augments the expression of IL-2 receptor (CD25) on human peripheral blood mononuclear cells (PBMC), cultured with tetanus toxoid. These properties of IMREG-1 are attributable to the peptides Tyr-Gly and Tyr-Gly-Gly which are identical to the N-terminal end of the enkephalins and represent final cleavage products of the proopiomelanocortin pathway. We examined the ability of IMREG-2 to regulate CD25 expression on PBMC exposed to tetanus toxoid and to modulate DTH responses to recall antigen.

RESULTS: IMREG-1 and IMREG-2 are able to augment human DTH responses to recall antigens and to enhance the expression of CD25 on antigen-stimulated PBMC in a concentration-dependent manner. Moreover, we were able to show recovery of the expression of CD25 on CD4+ lymphocytes obtained from HIV+ immunocompromised patients, after these patients had received biweekly IMREG-1 or IMREG-2 therapy over a period of several months.

CONCLUSIONS: We conclude that IMREG-1 and IMREG-2 both enhance CMI. We believe that either may be used therapeutically in conditions where CMI is impaired, e.g. with immunocompromised HIV-infected patients where clinical benefits of IMREG-1 have previously been described in a double-blind randomized placebo-controlled, clinical trial.

Keywords: AEGIS, Lymphokines, Immunity, Cellular, Immunization, HIV Infections, Double-Blind Method, Adjuvants, Immunologic, CD4-Positive T-Lymphocytes, Tetanus Toxoid, Antigens, Immunocompromised Host, Receptors, Interleukin-2, IMREG-1, Human, In Vitro, therapy, immunology, drug therapy, ICA11

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TuA270