Arachidonic acid metabolism is altered in sarcoid alveolar macrophages,

Macrophages produce various arachidonic acid (AA) metabolites which may either enhance or suppress inflammatory processes. We investigated AA metabolite production by alveolar macrophages (AMs) from 11 patients with pulmonary sarcoidosis and 9 normal volunteers. We assessed the production of both cyclooxygenase products (prostaglandin (PG) E2, thromboxane B2 (TXB2), PGF2[alpha], and 6-keto-PGF1[alpha]) and lipoxygenase products (leukotrienes (LT) and hydroxyeicosatetraenoic acids (HETEs)) in AM cultures. We found that sarcoid AMs produced less PGE2, TXB2, 6-keto-PGF1[alpha], and HETEs in both the unstimulated and the calcium ionophore-stimulated states compared with normal AMs. Sarcoid AMs also produced less PGF2[alpha] and LTs in the unstimulated state after 1 hr of incubation, but following calcium ionophore stimulation, these differences did not achieve statistical significance. We conclude that sarcoid AMs have a reduced capacity to produce AA metabolites compared with that of normal AMs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26855/1/0000420.pd

Renal cell carcinoma induces interleukin 10 and prostaglandin E2 production by monocytes

Immunotherapy with interleukin 2 (IL-2) is not an effective anti-cancer treatment in the majority of patients with renal cell carcinoma (RCC), suggesting that the activation of cytotoxic T cells or NK cells may be impaired in vivo in these patients. The production of immunosuppressive factors by RCC was investigated. Using immunohistochemistry, IL-10 was detectable in 10 of 21 tumour samples tested. IL-10 was undetectable in the supernatant of cell lines derived from these RCCs. However, these cell lines or their conditioned medium (RCC CM), but not normal renal epithelial cells adjacent to the RCC or breastcarcinoma cell lines, were found to induce IL-10, as well as prostaglandin E2 (PGE2) and tumour necrosis factor (TNF)α production by autologous or allogeneic peripheral blood mononuclear cells (PBMCs) and monocytes. IL-10 production induced by RCC CM was found to be dependent on TNF-α and PGE2 since an anti-TNF-α antibody (Ab) inhibited 40–70% of IL-10 production by monocytes, and the combination of anti-TNF-α Ab and indomethacin, an inhibitor of PGE2 production, inhibited 80–94% of RCC CM-induced IL-10 production by monocytes. The RCC CM of the five cell lines tested were found to induce a down-regulation of the expression of HLA-DR and CD86, as well as a strong inhibition of mannose receptor-dependent endocytosis by monocytes. The blockade of HLA-DR and CD86 expression was partially abrogated by indomethacin and anti-IL-10 Ab respectively, and completely abrogated by an anti-TNF-α Ab. The inhibition of mannose receptor-dependent endocytosis was partially abrogated by an anti-IL-10 Ab and completely abrogated by an anti-TNF-α Ab. These esults indicate that RCCs induce IL-10, PGE2 and TNF-α production by monocytes, which down-regulate the expression of cell-surface molecules involved in antigen presentation as well as their endocytic capacity. © 1999 Cancer Research Campaig