Biomedical subjects

M H Oppenheim

Publications and source records attributed to M H Oppenheim.

3 recordsLinked to original sources

PubMed1991

Ocular inflammation stimulated by intravitreal interleukin-8 and interleukin-1.

Interleukin-8 (IL-8), a cytokine with neutrophil chemotactic and activating properties, is known to be stimulated by IL-1. Fischer rats are more resistant to inflammation than Lewis rats probably due to a higher corticosteroid stress response. To determine the role of IL-8 in ocular inflammation, the effect of intravitreal injection of IL-8 was compared with that of IL-1 in both Lewis and Fischer rats. The IL-8, IL-1 alpha, or sterile balanced salt solution (control) was injected into one eye of each animal. Both IL-8 and IL-1 alpha caused inflammation in the eye of both strains, as detected by leukocyte counts of the anterior chamber and histopathologic examination. The eyes of animals injected with a cytokine had significantly higher numbers of leukocytes compared with eyes of control animals. Histopathologic examination confirmed these findings. The IL-1 alpha induced inflammation more consistently and more severely than the most effective dose of IL-8. This finding agreed with the concept of IL-1 initiating a cascade of inflammatory mediators including IL-8, which acts more specifically on a smaller population of leukocytes. A contralateral response was observed in the uninjected eye of experimental and control animals. The contralateral response in animals receiving the cytokines was significantly greater than that in controls. Lewis rats show a higher inflammatory response to the injections than do the Fischer rats. These data suggest that IL-8 may be active as one component in neutrophil-mediated ocular inflammation.

Animals↗

PubMed1985

Cytotoxicity of human serum for Leishmania donovani amastigotes: antibody facilitation of alternate complement pathway-mediated killing.

Mechanisms that mediate recovery from leishmanial infection have not been fully characterized but are generally believed to involve interactions between T lymphocytes and macrophages. A major role for serum-mediated effector mechanisms in the protection of humans from reinfection with Leishmania, however, has not been ruled out. In this report, amastigotes of L. donovani were incubated with dilutions of serum from normal subjects and from patients with kala-azar. Normal serum was cytotoxic for parasites at a dilution of greater than or equal to 1:20. Cytotoxicity did not occur in the presence of EDTA, was abolished by heating serum to 56 degrees C for 30 min, and was not diminished by prior adsorption of normal serum with parasites at 0 degree C. Killing proceeded normally in the presence of magnesium-ethylene glycol-bis(beta-aminoethyl ether)-N, N-tetraacetic acid, however, and was fully effected by C2-deficient serum. These studies indicated that killing of amastigotes, unlike that of promastigotes, was mediated via the alternate pathway of serum complement. In further studies, cytotoxicity of normal serum was enhanced three- to fivefold by factors in patient serum. This enhanced cytotoxicity also proceeded via the alternate complement pathway. Factors that enhanced cytotoxicity were characterized as parasite-specific immunoglobulin G: they eluted with immunoglobulin G on column chromatography, were adsorbed by immobilized staphylococcal protein A, and were not removed from the parasite surface by extensive washing. Thus, infection of individuals with L. donovani resulted in the production of a new, qualitatively and quantitatively distinct immune mechanism directed against the amastigote form of the parasite, namely, antibody-directed, alternate complement pathway-mediated cytotoxicity. These results provide a mechanistic framework for a role of humoral factors in human resistance to reinfection with L. donovani.

Animals↗

PubMedDate not supplied

Interleukin-2: solid-tumor therapy.

Interleukin-2 (IL-2) is a soluble factor produced by T cells that stimulates growth and activity of lymphocytes and other immune cells. First noted in murine studies, the antitumor efficacy of IL-2 has been shown to induce partial and complete regression of some tumors in human clinical trials over the past decade. Although the initial clinical success of IL-2 was in combination with lymphokine-activated killer cells, IL-2 alone has subsequently been shown to be equally efficacious. Combinations of cytokines and chemotherapies with IL-2 have been generally inconclusive and disappointing with the possible exception of interferon-alpha. Toxicities of IL-2 are common and often dose limiting. Symptomatic therapy has allowed patients to tolerate somewhat higher doses, but has not addressed the underlying mechanisms of these toxicities which may involve mediators such as tumor necrosis factor, interferon-gamma, and nitric oxide. Clinical studies assessing these factors for their involvement in the antitumor effects of IL-2 as well as its toxicities may allow better understanding of IL-2, and perhaps lead to improved cancer therapies.

Animals↗