A novel epitope R7V common to all HIV-1 isolates is recognized by neutralizing IgG found in HIV-infected patients and immunized rabbits.

We have previously reported that the presence of antibodies (Ab) directed to the beta2-microglobulin-derived peptide R7V in patient's serum correlated with the nonprogression to AIDS. In order to investigate whether R7V motif could represent a potential target for neutralization, we have immunopurified anti-R7V Ab from sera of nonprogressors, as well as from sera of rabbits injected with R7V. We showed that human as well as rabbit purified,anti-R7V IgG precipitated laboratory adapted strains, as well as primary isolates from different clades indicating that: (1) R7V epitope is a common motif presented at the surface of genetically divergent HIV-1 strains (2) R7V is immunogenic in vivo.

Rationale for a vaccine using cellular-derived epitope presented by HIV isolates.

It has been clearly demonstrated that cellular antigens (HLA, beta 2-microglobulin) are incorporated at the virion surface. The same epitope derived from beta 2-microglobulin is presented on all virus isolates. The peptide was identified by blocking the neutralizing capacity of a monoclonal antibody directed to R7V epitope: using this peptide for developing an ELISA, we have detected antibodies in nonprogressor patients with neutralizing property to laboratory strains and primary isolates.

Circulating cell adhesion molecules in HIV1-infected patients as indicator markers for AIDS progression.

Cell adhesion molecules play an important role during immune responses. Circulating (c) forms of these molecules have been used as monitors of disease progression. In this study, we have investigated serum levels of ICAM1, ICAM2, ICAM3 and VCAM1 in HIV-infected patients.

Regulation of lipopolysaccharide-induced tumor necrosis factor production by cyclosporin A in mice primed with muramyl dipeptide.

The effect of cyclosporin A (CsA) on tumor necrosis factor (TNF) or interleukin-6 (IL-6) production was evaluated in vivo in primed or unprimed mice challenged with lipopolysaccharide (LPS). Both pretreatment with BCG infection or with muramyl dipeptide (MDP) prior to LPS challenge resulted in an increase in the cytokine bioactivity level in the blood. CsA administration inhibited the TNF production.

Differential role of interferon-gamma in the potentiating effect of muramyl peptides for enhanced responses to lipopolysaccharide in mice: effect of cyclosporin A.

Cyclosporin A (CsA) administration reduced mortality in mice sensitized to endotoxic toxicity by various agents, such as muramyl dipeptide (MDP) or a lipophilic derivative. CsA is an inhibitor of a variety of T cell responses, suggesting that muramyl peptides could influence LPS-induced effects via the release of lymphokine. The potentiation of TNF production by pretreatment with muramyl peptides was comparable in nude mice and in controls, indicating that it is a T-independent mechanism, and CsA produced a similar inhibition in both groups.

Selective modulation of lipopolysaccharide-induced death and cytokine production by various muramyl peptides.

Pretreatment of animals with the adjuvant muramyl dipeptide enhances both the production of circulating tumor necrosis factor and the sensitivity to the lethal effect of a lipopolysaccharide (LPS) challenge. The present study examined the capacity of various adjuvant muramyl dipeptide derivatives to potentiate responsiveness to LPS administration. Cytokine levels in serum were determined at various time intervals after LPS administration by bioassays and immunoassays; the cytokines examined were tumor necrosis factor, interleukin-1, interleukin-6, and gamma interferon.

Modulation of lipopolysaccharide-induced cytokine gene expression in mouse bone marrow-derived macrophages by muramyl dipeptide.

Previous studies have shown that an i.v. injection of muramyl dipeptide (MDP) before a LPS challenge strongly potentiated serum TNF and IL-6 release in mice.

Indirect and selective down-regulation of serum tumor necrosis factor-alpha release by interleukin-1 beta.

A selective inhibition of LPS-induced tumor necrosis factor-alpha (TNF) response in mice was caused by an injection of recombinant human interleukin-1 (IL-1). The decrease in serum TNF level reached 70 to 80 percent of the controls receiving LPS alone when IL-1 was given simultaneously or prior to the challenge. At the same time serum IL-6 release was more elevated.

Influence of endogenous glucocorticoid on endotoxin-induced production of circulating TNF-alpha.

Mice are quite resistant to LPS toxicity but even a small dose induced a monophasic production of circulating TNF. In BCG-treated mice challenged with LPS, the greater susceptibility was associated with the capacity of producing elevated levels of TNF in the blood. During pregnancy, after adrenalectomy, and particularly after treatment with galactosamine, smaller amounts of LPS were lethal in mice.

Differential priming for endotoxin-induced circulating cytokine production by tumor necrosis factor-alpha and interleukin 1 beta.

In unprimed mice, a single injection of a non-lethal dose of lipopolysaccharide (LPS) produced a rise in tumor necrosis factor (TNF) and interleukin 6 (IL 6) activities. Peak serum concentrations were attained, respectively, 1.5 hr and 2.