Wide variation in lymphocyte steroid sensitivity among healthy human volunteers

Steroids are frequently used to treat inflammatory conditions in which lymp hocytes play a role. We have recently shown that in severe ulcerative colit is, treatment outcome correlates better with in vitro estimates of lymphocy te steroid sensitivity (LSS) than with disease severity. This lead us to ex amine the range and variability of LSS in the healthy population. Dexamethasone inhibition of lymphocyte proliferation was measured on 54 occ asions in 18 volunteers (mean age, 46 yr; range, 25-60 yr) over an 8-month period. Inter- and intra-assay variation in LSS was low when expressed as m aximum inhibition achieved, I-max (2.9% and 3.4%, respectively), allowing u s to demonstrate a very wide variation in I-max between healthy individuals (-6.7% to 99.7%). In contrast, within-individual variation of I-max was si gnificantly less than between-individual Variation (F test, P < 0.0001), co nsistent with stability of this parameter over time. No correlation was see n between. LSS and glucocorticoid receptor density or affinity, suggesting a postreceptor mechanism. Serum cortisol at the time of sampling and skin s ensitivity to glucocorticoids also failed to correlate with LSS. This study suggests I-max is a sufficiently stable parameter to categorize healthy individuals according to LSS. The nide range of LSS demonstrated is striking and suggests that up to 30% of the healthy population would fail to respond to steroid therapy for severe inflammatory conditions.