Phytohaemagglutinin stimulation of lymphocytes in infections due to pseudomonas aeruginosa

Abstract

Abstract Clinical observations and results of several authors as well as our prior examinations refer to a reduced immune responsiveness in patients suffering from Pseudomonas aeruginosa infections (2,10,14,15,16,17,18, 35, 39, 43). However, these literary data provide either indirect proves of the immune suppressive effect of P. aeruginosa on the basis of clinical experiences, or they are based on in vitro and animal experiments. That is why a direct proof of this phenomenon during the different stages of Pseudomonas infections in man is still lacking. In order to obtain evidence and to explain the background as well as the dynamics of the decreased immune responsiveness, we longitudinally followed (i. e. in subsequent stages of these infectious complications) the reactivity of lymphocytes (Ly) to phytohaemagglutinin (PHA) on 67 occasions in 17 patients suffering from P. aeruginosa infections. Five of them had mild, two moderately severe, five serious and five lethal infectious complications (see Download : Download full-size image ). In eight patients sepsis developed also. No difference was found in the response to PHA of the healthy controls and of patients still free of infection (see Download : Download full-size image ). But the rate of blast transformation decreased significantly at the onset of complications. Later, during ongoing complications, still only one third of the normal dpm (desintegration per minute) values could be found. The lowest values were measured when sepsis or septic shock state developed. During improvement and convalescence the response increased and reached nearly the complication-free values after complete recovery. In about half of the severe septic shock states the PHA response disappeared completely. However, in surviving patients, the transformability of the Ly-s returned to normal values, or even exceeded the normal average when the shock or sepsis was over. Download : Download full-size image shows the changing dpm values in such a case. When the Ly-s were cultured in parallel in autologous and AB plasma, the average of blast transformation in the latter exceeded significantly that of the former one, but still remained under the normal level. From several plasma factors, which may depress Ly transformation upon PHA effect, non-protein nitrogen (NPN), IgM and α2-globulin were measured longitudinally too (see Download : Download full-size image ). In patients with an elevated α2-globulin together with another humoral factor (high IgM or NPN value) a reduced thymidine incorporation was always measured. All these data demonstrate clearly, that infections due to P. aeruginosa are accompanied by a reduced immune responsiveness in man also. The antigenic effect of P. aeruginosa results in reducing the reactivity of the Ly-s to PHA probably through the activation of the non-specific suppressor T cell system (4, 7, 19, 20, 30, 41, 46) at the onset of the infection. With the development of the inflammatory process, ongrowing humoral factors (NPN, IgM, α2-globulin) exert an immunosuppressive effect. In septic shock state the antigen-overload and the humoral factors acting very much alike together cause the complete disappearance of Ly reactivity. Thus, in P. aeruginosa infections both exogenic (bacterial) and endogenic (humoral) factors are responsible for the impaired immune responsiveness.