The prooxidant state and psychologic stress: response to Chalmers et al. (Perspectives / Correspondence).

We thank Chalmers et al. for their interest in our paper punished in EHP (1). We also thank them for sharing their earlier studies on free radical-mediated reduction of lymphocytic 5'-ectonucleotidase (NT) activity during psychologic stress (2-4) and on the reduction of this activity during HIV infection and diabetes (4,5), which were reported to be associated with a high prooxidant state.

Their works have actually shown that psychologic stress results in a decreased NT activity and in a decreased tissue ascorbate that can both be normalized by antioxidant intake or when the stress resolved. Thereby, Chalmers et al. suggest that psychologic stress itself can cause an increased prooxidant state responsible for decreased NT activity, which may contribute to the immune deficiency reported in stressed or depressed patients. They thus propose that a decrease in NT activity may be a good marker of a prooxidant state in humans (2-4).

In agreement with their hypothesis, our population-based study underlined that, independently of other studied factors and in particular of tobacco smoking, psychologic stress truly contributes to a decrease in the overall antioxidant capacity of healthy subjects as measured by means of the free radical-mediated hemolysis test (Spiral's KRL test) (6,7). Furthermore, our results indicated that among the studied factors and besides cigarette smoking, psychologic stress was the lifestyle factor that was most markedly associated with a decreased antioxidant capacity (1). Thus, in accordance with reports from Chalmers et al. (5), Niki (8) and Young and Woodside (9) suggest that psychologic stress can induce per se an unbalanced antioxidative homeostasis leading to the occurrence of oxidant stress that may increase the incidence of free radical-mediated diseases such as cancer, cardiovascular diseases, diabetes, inflammatory diseases, and HIV infection.

It is noteworthy that the aim of our study was to evaluate lifestyle factors that may contribute to the normal variability of the overall antioxidant status in healthy subjects. Because of the involvement of numerous studied lifestyle factors in the variability of the overall antioxidant status evaluated in our study, we did not thoroughly discuss oxidant stress probably caused by psychologic stress or emphasize the major importance of the potential involvement of psychologic stress in human disease. Although we have not previously mentioned the works of Chalmers et al. on the psychologic stress-mediated prooxidant state, we hope that these letters will highlight their studies.

Concerning the mechanism underlying psychologic stress-related oxidant stress described by Chalmers et al., we agree with their hypothesis of the involvement of a chronic elevation of cortisol favoring the development of an innate immune response at the expense of the humoral immune system, which results in chronic inflammatory process and therefore in a high prooxidant state. Whether the inhibition of cortisol action as compared to antioxidant therapy could reduce the prooxidant state induced by psychologic stress remains to be determined. Moreover, according to Chalmers et al. (4), lymphocytic NT activity appears to be a good marker of oxidant stress. Additional clinical designs are now needed to confirm the use of this assay as a biomarker of a prooxidant state. The use of the hemolysis test in combination with analytic dosages of specific biomarkers of antioxidant and prooxidant states could be helpful for this purpose.

In conclusion, in light of Chalmers and coworkers' findings (3,4) and of our own findings (1), psychologic stress effects, which are often underestimated, should be taken into account among healthy control subjects and among patients bearing free radical-mediated disease in clinical and epidemiologic trials. In particular, regarding Chalmers et al.'s study that showed a reduced NT activity probably related to oxidant stress during HIV infection (5), it should be determined whether psychologic stress is responsible for an oxidant stress-mediated increase in immune deficiency resulting from HIV infection. Indeed, investigations on the potential involvement of psychologic stress in human free radical-mediated and degenerative disease are still too scarce, and Chalmers et al. are right in emphasizing the major potential influence of psychologic stress.

Phillipe Durand
Centre Europeen de Recherche
et d'Analyse
Dijon, France

Marie-Pascale Lehucher-Michel
Consultation de Hospitaliere de Pathologies
Professionnelles
Service de Medecine du Travail
Marseille, France
E-mail: [e-mail]

REFERENCES AND NOTES

(1.) Lesgards J-F, Durand P, Lassarre M, Stocker P, Lesgards G, Lanteaume A, Prost M, Lehucher-Michel M-P. Assessment of lifestyle effects on the overall antioxidant capacity of healthy subjects. Environ Health Perspect 110:479-486 (2002).

(2.) Blake-Mortimer JS, Winefield AH, Chalmers AH. The relationship between 5'-ectonucleotidase and psychological stress. Int J Stress Manage 3:189-207 (1996).

(3.) Blake-Mortimer JS, Winefield AH, Chalmers AH. Evidence for free radical-mediated reduction of lymphocytic 5'-ectonucleotidase during stress. Int J Stress Manage 5:57-75 (1998).

(4.) Chalmers AH, Blake-Mortimer JS, Winefield AH. Lymphocytic 5'-ectonucleotidase, an indicator of oxidative stress in humans. Redox Report 5:89-91 (2000).

(5.) Chalmers AH, Hare C, Wooley G, Frazier IH. Lymphocyte ectoenzyme activity compared in healthy persons and patients seropositive to or at high risk of HIV infection. Immunol Cell Biol 68:81-85 (1990).

(6.) Prost M. Process for the determination by means of free radicals of the antioxidant properties of a living organism or potentially aggressive agents. U.S. patent no. 5,135,850. Washington, DC:U.S. Patent and Trademark Office, 1990. Available: http://patft.uspto.gov/netacgi/ nph-Parser?patentnumber=5135850 [cited 18 November 2002].

(7.) Blache D, Prost M. Free radical attack: biological test for human resistance capability. In: Proceedings of the IX College Park Colloquium on Chemical Evolution: A Lunar-Based Chemical Analysis Laboratory (Ponnamperuma C, Gehrke W, eds). Washington, DC:NASA, 1992;82-98.

(8.) Niki E. Free radicals in the 1900's: from in vitro to in vivo. Free Radic Res 33:693-704 (2001).

(9.) Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 54:76-86 (2001).