Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suppressor monocytes have been found in a number of human diseases most of which are associated with lymphopenia and deficiences in cell mediated immunity. In our studies both quantitative and qualitative differences in monocytes were detected in certain patients with advanced Hodgkin's disease or tuberculosis. In certain patients lymphocyte activating factor production by monocytes was severely depressed in part secondary to decreased activation by suppressed T cells, although at times primary impairment of macrophage function was also probably contributory. Mononuclear cell cultures from patients with advanced Hodgkin's disease also manifested excessive prostaglandin secretion; however, the association of this with monocyte suppression and deficient LAF production was inconstant. Furthermore, reversibility of monocyte suppression could not regularly be achieved by inhibition of prostaglandin synthetase with indomethacin suggesting that excessive production of prostaglandins is unlikely to be the sole mechanism of monocyte inhibition of lymphoproliferation. It also remains to be established whether the inhibition of lymphoproliferation in vitro is important to in vivo delayed hypersensitivity or whether the mechanism is related to other macrophage effects such as tumor cytostasis and cytolysis.
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PMID:Suppressor monocytes in human disease: a review. 16 50

Indomethacin significantly enhances the depressed levels of lymphocyte proliferation to the mitogens phytohemagglutinin and concanavalin A in melanoma patients. We postulated that these results were related to an abnormality in prostaglandin E2 (PGE2)-mediated suppression, since this mechanism has previously has previously been demonstrated in patients with Hodgkin's lymphoma and with head and neck carcinoma. However, the results of three experimental approaches did not support this hypothesis. First, in vitro PGE2 production by cultured blood mononuclear cells was the same in 16 melanoma patients as in 45 normal controls (4.9 versus 4.7 ng/ml). Second, lymphocyte sensitivity to PGE2 for melanoma patients was essentially the same as that for normal controls, since exogenous doses of PGE2 inhibited the mitogen responses to the same degree. Third, another prostaglandin synthetase inhibitor (RO-205720), which is structurally unrelated to indomethacin, did not augment the mitogen response in these patients. Thus PGE2 cannot be implicated as a mediator of immunosuppression in melanoma patients. To further examine the immunomodulatory mechanism of indomethacin, we preincubated the drug with purified populations of either lymphocytes or monocytes, which were then recombined and tested for mitogen response. The results suggested that indomethacin had a direct effect on the responding T lymphocytes rather than an indirect effect on monocytes. These are the first studies demonstrating that indomethacin can act directly as a modulator of cellular immune function, independent of PGE2-mediated suppression.
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PMID:Immune modulatory effects of indomethacin in melanoma patients are not related to prostaglandin E2-mediated suppression. 628 58