Synergistic effect of cortisol and prostaglandin E2 on the PHA response. Relation to immunosuppression induced by...

Surgical and thermal trauma in man are followed by depressed immunological responses in vivo and reduced lymphocyte reactivity in vitro. The possibility that these are related to trauma-induced rises in tissue levels of cortisol and prostaglandins was examined by studying the effect of a wide range of concentrations of cortisol and prostaglandin E2 (PGE2), separately and together on the phytohaemagglutinin (PHA) response of human peripheral blood lymphocytes. These effects were plotted on two-dimensional dose:effect graphs; the shapes of the curves connecting combinations of equal effect (isoboles) showed that these agents acted with marked synergy in suppressing the response, provided they were present while the response was taking place. Synergy was also shown by using a simple equation relating the concentrations of the agents producing a given effect when used in combination to the concentrations needed to produce the same effect when used separately. Cortisol at concentrations reached in the peripheral blood after trauma in man (1-4 X 10(-6)M) and PGE2 at concentrations to be expected in traumatized tissues (up to 4 X 10(-7)M) each suppressed the response only slightly. The former reduced the response to 0-7 of controls and the latter 0-5 (means of seven subjects). When both were present together at these concentrations, the response was markedly depressed (mean 0-06, range 0-02--0-13 of controls). However, when lymphocytes were incubated at 37 degrees C with cortisol and PGE2 for 20 hr and then washed before exposure to PHA, the response was not inhibited, even by substantially higher concentrations than the above, and was usually moderately enhanced. Therefore, these in vitro experiments do not explain the depressed PHA response observed in peripheral blood lymphocytes after trauma. It is possible, however, that raised cortisol and prostaglandin levels depress the reactivity of lymphocytes while they remain in the traumatized region and its lymph drainage area.