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

Tumor necrosis factor stimulates interleukin-1 and prostaglandin E2 production in resting macrophages

We have investigated the effect of tumor necrosis factor on the release of interleukin-1 and PGE2 from murine resident peritoneal macrophages. Tumor necrosis factor causes an increase in the production of interleukin-1 and PGE2 with a maximum induction for both noted at 5.9 x 10-8M. While indomethacin decreased tumor necrosis factor induced PGE2 production, this cyclooxygenase inhibitor augmented tumor necrosis factor induced interleukin-1 production. Our data suggests that tumor necrosis factor may be an important immunopotentiating agent in addition to its previously described cytolytic and metabolic activities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26197/1/0000276.pd