Immunology Letters, 30 (1991) 141-142
Elsevier IMLET 01663 Letter to the Editor
Stress influences C D 4 ÷ lymphocyte counts L a m b e r t u s J. H. van Tits ~ a n d Sietze J. G r a a f s m a 2
(Received 14 June 1991; accepted 20 June 1991)
Under pressure brought by organizations supporting the patients' interest and by the media, medical treatments of human immunodeficiency virus (HIV)-infected patients are instituted prior to exact knowledge of their merits. Since development of the acquired immunodeficiency syndrome (AIDS) in HIV-positive patients is characterized by a progressive depletion of CD4 ÷ (helper/inducer) lymphocytes, the CD4 ÷ cell count is a decisive factor in medication. In persons with asymptomatic HIV infection, zidovudine therapy has been recommended when the CD4 ÷ cell count reaches values below 500//~1 [1]. No attention has been paid to the circumstances under which blood should be withdrawn and the number of measurements necessary. A clear definition of these circumstances appears to be necessary, since circulating lymphocyte numbers can be influenced by the sympathetic nervous system [2]. We used isoproterenol infusion (3.5, 7, 17.5, 35 and 70 ng/kg/min for 5 min each) in 14 normal healthy volunteers as a model to investigate sympathetic influences on circulating lymphocyte numbers. Whereas the percentage of pan-T cells had not changed, the absolute number had significantly increased after infusion of isoproterenol. Within the population of T cells, only the number of CD8 ÷ (suppressor/cytotoxic) cells increased (from 523 ___41 to 997 + 64 cells//zl). On the other hand, the number of CD4 ÷ cells significantly decreased from 839 + 73 to 494_+43 cells//~l. In fact, 8 subjects had a CD4 ÷ cell count below 500, 5 of them even below 400. The C D 4 + / C D 8 + ratio decreased from 1.6_+0.1 to 0.5 _+0.1. Similar changes in circulating lymphocyte numbers have been reported after mental stress or after dynamic exercise [3, 4], and could be attributable to the adrenergic system. Furthermore, the spleen seems to play a major role in this process [5].
Thus, acute stress-induced increases in plasma catecholamines might lead to false estimations of lymphocyte numbers, and zidovudine therapy of HIV-positive patients may be started too early. Because of the potential development of resistance to zidovudine and the limited duration of therapy with regard to the side effects, the timing of zidovudine therapy is very important. We conclude that more attention should be paid to the conditions (physical as well as mental) under which blood is withdrawn for monitoring lymphocyte numbers and recommend that a rest period of at least 15 minutes be observed; this is also routine for the determination of plasma catecholamines. Lambertus J. H. van Tits 1 Sietze J. Graafsma 2
1Biochemical Research Laboratories, Medical Clinic and Polyclinic, Division of Renal and Hypertensive Diseases, University of Essen, Essen, F.R.G. and 2Department of Internal Medicine, Division of General Internal Medicine, Nijmegen, The Netherlands
References
[1] Volberding,P. A., Lagakos, S. W., Koch, M. A. et al. (1990) N. Engl. J. Med. 322, 941. [2] Crary,B., Hauser, S. L., Borysenko,M., Kutz, I., Hoban, C., Ault, K. A., Weiner,H. L. and Benson,H. (1983)J. Immunol. 131, 1178.
0165-2478 / 91 / $3.50 © 1991 ElsevierSciencePublishers B.V.All rights reserved.
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[3] Landmann, R. M. A., Mfiller, E B., Perini, C., Wesp, M., Erne, P. and Biihler, E R. (1984) Clin. Exp. Immunol. 58, 127. [4] Maisel, A. S., Knowlton, K. U., Fowler, P., Rearden, A., Ziegler, M. G., Motulsky, H. J., Insel, E A. and Michel, M. C.
142
(1990) J. Clin. Invest, 85, 462. [5] Van Tits, L. J. H., Michel, M. C., Grosse-Wilde, H., Happel M., Eigler, E-W., Soliman, A. and Brodde, O.-E. (1990) Am J. Physiol. (Endocrinol. Metab.) El91.
Elsevier IMLET 01663 Letter to the Editor
Stress influences C D 4 ÷ lymphocyte counts L a m b e r t u s J. H. van Tits ~ a n d Sietze J. G r a a f s m a 2
(Received 14 June 1991; accepted 20 June 1991)
Under pressure brought by organizations supporting the patients' interest and by the media, medical treatments of human immunodeficiency virus (HIV)-infected patients are instituted prior to exact knowledge of their merits. Since development of the acquired immunodeficiency syndrome (AIDS) in HIV-positive patients is characterized by a progressive depletion of CD4 ÷ (helper/inducer) lymphocytes, the CD4 ÷ cell count is a decisive factor in medication. In persons with asymptomatic HIV infection, zidovudine therapy has been recommended when the CD4 ÷ cell count reaches values below 500//~1 [1]. No attention has been paid to the circumstances under which blood should be withdrawn and the number of measurements necessary. A clear definition of these circumstances appears to be necessary, since circulating lymphocyte numbers can be influenced by the sympathetic nervous system [2]. We used isoproterenol infusion (3.5, 7, 17.5, 35 and 70 ng/kg/min for 5 min each) in 14 normal healthy volunteers as a model to investigate sympathetic influences on circulating lymphocyte numbers. Whereas the percentage of pan-T cells had not changed, the absolute number had significantly increased after infusion of isoproterenol. Within the population of T cells, only the number of CD8 ÷ (suppressor/cytotoxic) cells increased (from 523 ___41 to 997 + 64 cells//zl). On the other hand, the number of CD4 ÷ cells significantly decreased from 839 + 73 to 494_+43 cells//~l. In fact, 8 subjects had a CD4 ÷ cell count below 500, 5 of them even below 400. The C D 4 + / C D 8 + ratio decreased from 1.6_+0.1 to 0.5 _+0.1. Similar changes in circulating lymphocyte numbers have been reported after mental stress or after dynamic exercise [3, 4], and could be attributable to the adrenergic system. Furthermore, the spleen seems to play a major role in this process [5].
Thus, acute stress-induced increases in plasma catecholamines might lead to false estimations of lymphocyte numbers, and zidovudine therapy of HIV-positive patients may be started too early. Because of the potential development of resistance to zidovudine and the limited duration of therapy with regard to the side effects, the timing of zidovudine therapy is very important. We conclude that more attention should be paid to the conditions (physical as well as mental) under which blood is withdrawn for monitoring lymphocyte numbers and recommend that a rest period of at least 15 minutes be observed; this is also routine for the determination of plasma catecholamines. Lambertus J. H. van Tits 1 Sietze J. Graafsma 2
1Biochemical Research Laboratories, Medical Clinic and Polyclinic, Division of Renal and Hypertensive Diseases, University of Essen, Essen, F.R.G. and 2Department of Internal Medicine, Division of General Internal Medicine, Nijmegen, The Netherlands
References
[1] Volberding,P. A., Lagakos, S. W., Koch, M. A. et al. (1990) N. Engl. J. Med. 322, 941. [2] Crary,B., Hauser, S. L., Borysenko,M., Kutz, I., Hoban, C., Ault, K. A., Weiner,H. L. and Benson,H. (1983)J. Immunol. 131, 1178.
0165-2478 / 91 / $3.50 © 1991 ElsevierSciencePublishers B.V.All rights reserved.
141
[3] Landmann, R. M. A., Mfiller, E B., Perini, C., Wesp, M., Erne, P. and Biihler, E R. (1984) Clin. Exp. Immunol. 58, 127. [4] Maisel, A. S., Knowlton, K. U., Fowler, P., Rearden, A., Ziegler, M. G., Motulsky, H. J., Insel, E A. and Michel, M. C.
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(1990) J. Clin. Invest, 85, 462. [5] Van Tits, L. J. H., Michel, M. C., Grosse-Wilde, H., Happel M., Eigler, E-W., Soliman, A. and Brodde, O.-E. (1990) Am J. Physiol. (Endocrinol. Metab.) El91.
