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Exercise to Increase Lymphocyte Activation After Chemo

THE USE OF EXERCISE TO INCREASE LYMPHOCYTE ACTIVATION FOLLOWING CHEMOTHERAPY FOR BREAST CANCER

A. M. Mastro, N. A. Hutnick, N. I. Williams, W. J. Kraemer, R. H. Dixon, and A. D. Bleznak

Pennsylvania State University, University Park, PA; University of Connecticut, Storrs, CT; Center Medical and Surgical Associates, Mt. Nittany Medical Center, State College, PA

E-mail: a36@psu.edu

Chemotherapeutic drugs commonly used to treat breast cancer also target lymphocytes. Lymphocyte populations are greatly reduced following chemotherapy; T helper cells can remain at low levels for many years. In addition, the remaining T cells may be less functional, as suggested by suppressed levels of mitogen activation.

Exercise has been shown to have many benefits for cancer patients during and following chemotherapy such as an increase in psychological and physical function, as well as reduced neutropenia, thrombopenia, pain, and hospitalization time.

Moreover, AIDS patients on a six month mixed exercise program exhibited an increase in T helper cells. We hypothesized that exercise intervention would increase the function of lymphocytes in breast cancer patients following chemotherapy.

Methods: One group of breast cancer patients (N=28, Mean age 48.5 yrs) was enrolled in an exercise intervention while another group (N-21, mean age 52.3 years) had none. Blood was taken before and after chemotherapy, three months after treatment (mid-intervention) and six months after treatment (end of intervention).

Flow cytometry was used to determine the number of CD4+ and activated, CD69+, T cells. Blood was cultured with the mitogens phytohemagglutinnin, concanavalin A, or pokeweed mitogen, and DNA synthesis measured by tritiated thymidine incorporation. Plasma interleukin 6 (IL-6) and interferon gamma (IFN-ã) were measured by ELISA.

Statistical analyses were performed using SPSS. Changes within a group over time were determined using the Wilcoxon Signed Rank Test. The Mann Whitney U test was used to compare the exercisers and non-exercisers.

Results: The exercisers showed an increase in VO2 max, and upper body strength. They also had a greater number of activated (CD4+CD69+) T cells and higher levels of lymphocyte proliferation at the end of the intervention compared to non-exercisers. Mid-intervention, the concentration of plasma IFN-ã decreased in the exercisers while it increased in the non-exercisers.

There were no significant differences in IL-6 between the two groups. The IFN-ã/IL-6 ratio was elevated in the exercisers although it was not statistically different from the non-exercisers. However, there was a significant decrease in the IFN-ã/IL- 6 ratio of the exercisers following intervention.

Conclusions: A six-month exercise intervention following chemotherapy resulted in greater activation of T lymphocytes in breast cancer patients. Although not statistically different, the exercisers also showed an elevated IFN-ã/IL-6 ratio compared to the non-exercisers.

This ratio suggests an increased Th1 response characteristic of activation of the cellular immunity. The activation of T cells and the decrease in INF-ã as well as the IFN-ã/IL-6 ratio suggests that appropriate exercise can help the breast cancer survivor's immune system return to normal.

Original work supported by the U.S. Army Medical Research and Materiel Command under DAMD17- 98-1-8142 and current work supported by General Clinical Research Center of Penn State University, NIH M01 RR 10732; Penn State University’s President Fund for Research, and an NSF REU grant through the Nutrition Department IRB# 16051.

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