Muscle fibrosis and contractures in a pethidine addict.

sensitivity to P.P.D. (Field and Caspary, 1971a) yet negative Mantoux reaction also has a high level of serum depressive factor. The inhibitory factor is not specific, in so far as M.S. or sarcoid serum will also interfere with unrelated antigen-lympho-cyte interaction. For example, serum (1:60) from a patient with other neurological disease and two M.S. sera reduced a mixed lymphocyte reaction by 23-1, 28-6, and 41 5°% respectively. Likewise M.S. serum (1:60) reduced the interaction between bovine serum albumin and lymphocytes in a case of erythema nodosum by 54-8% and for egg albumen by 4810. A full account of these studies will be given elsewhere , but it is already clear that the development of lymphocyte sensitization (as indicated by the capacity to interact with a particular antigen) seems to be associated with the appearance in the serum of a depressant factor and that this factor is more effective against its own lymphocytes than those from another individual. In view of the many reports of depressive factor referred to in the introduction, it may be that the present study of M.S. and other neurological disease is but a special instance of a general phenomenon-the simultaneous development of lymphocyte responsiveness and a serum-mediated "damping mechanism." If further studies support this view, then we have another example of a biological "brake-accelerator" mechanism, operating this time in immunological reactivity. The suppressor element might indeed be the "feedback factor" postulated in several modern schemata involving lymphocyte activity-for example, that of Mackler (1971). It is legitimate to speculate that disease may result from imbalance between lymphocyte reactivity on the one hand and suppressive activity of serum on the other, so that it would be reasonable to attempt therapeutic control of lymphocyte activity (either in positive or negative direction) by increasing or reducing the suppressive factor. Thus autoimmune diseases (if they exist) presumably result from a runaway activity of lympho-cytes and might be treated by augmenting the level of suppressor factor. On the other hand, where lymphocyte activity is being held in check physiologically and where its greater exercise might be beneficial-for example, in resistence to cancer-it might be possible to eliminate or reduce suppressor activity. As a first step it is necessary to isolate and characterize the suppressor factor. Its relation to the factor isolated by Cooper-band, Bondevik, Schmid, and Mannick (1968) is being explored, but it is already clear that it occurs in the …