Antigen stimulation of prostaglandin synthesis and control of immune responses.

Abstract

Within 2 min following the intravenous injection of sheep erythrocytes (sRBC) there occurs 20 to 80-fold increase in prostaglandin (PG) F2alpha in the spleen. This burst of synthesis is followed by a slow decline to control levels over the next 1-4 hr. No increase in splenic PGF2alpha levels is observed between 24 and 72 hr after injection. Injection of colloidal carbon results in a small increase, approximately 20% of the increase in PGF2alpha observed with sRBC. The early increase in splenic PGF2alpha levels stimulated by sRBC is also dependent upon thymus-derived (T) cells, since the increase is small or nonexistent in athymic mice and NZB mice. Also, the elevation of splenic PGF2alpha levels is blocked by the administration of indomethacin or Ro 20-5720, both of which block the synthesis of prostglandin. A small increase (2-fold) in PGF2alpha levels occurs in the thymus. A soluble antigen, bovine gamma globulin, stimulated a bimodal increase in splenic PGF2alpha levels, the early peak occurring at 2 hr and the later increase occurring at 48 hr. Using inhibitors of prostaglandin synthesis, it is possible to enhance the appearance of cells forming 19S antibody against sRBC, both in vivo and in vitro. Furthermore, inhibition of prostaglandin synthesis enhances DNA synthesis induced in a two-way mixed-lymphocyte reaction only in whole spleen cell cultures and not in cultures of spleen cells purified by passage over glass wool. Based on this evidence, it is proposed that the prostaglandins represent a major soluble mediator in the control of T cell-T cell interactions and also play an important part in T-B (bone-marrow derived) cell interactions.

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

“…In our experiments when T cells were enriched (and B cells depleted) by passage over plastic bead columns, the inhibition curves of PGE~ and PGE2 on PWM approached the curves of the effects of these compounds on PHA-stimulated cells. There is some evidence in animals that PGs affect B-cell function, but there are no data in man (4,(30)(31)(32)(33). Further investigation of PG effects with other mitogens and on B-cell subpopulations may clarify this issue.…”

Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70.

“…The action of the prostaglandin-producing suppressor cell can be blocked in vitro (1)(2)(3) and in vivo (4-6) by administration of indomethacin, a prostaglandin synthetase inhibitor, with a resultant enhancement of humoral (4,5) and cellular (6) immune responses.…”

Regulation of human B cell activation by prostaglandin E2. Suppression of the generation of immunoglobulin-secreting cells.

“…The relationship of these various influences may contribute to the disparate influence of inhibitors of cyclooxygenase activity observed on various specific antibody responses in intact animals or humans. Thus, inhibitors of prostaglandin biosynthesis may augment the antibody response to sheep erythrocytes in mice (28). In humans, however, inhibitors of cyclooxygenase activity do not uniformly cause an increase in all antibody levels.…”

“…In vivo studies in mice showing that antibody responses could be significantly enhanced by cyclooxygenase inhibitors suggested a role for prostaglandins in regulating the generation of immunoglobulin-secreting cells (ISC) (28). In addition, in vivo studies in man indicate that administration of cyclooxygenase inhibitors may augment secondary responses to immunization with viral antigens while having no effect on primary responses (29).…”