title: Effect of millimeter waves on cyclophosphamide induced suppression of T cell functions.
abstract: The effects of low power electromagnetic millimeter waves (MWs) on T cell activation, proliferation, and effector functions were studied in BALB/c mice. These functions are important in T-lymphocyte mediated immune responses. The MW exposure characteristics were: frequency = 42.2 GHz; peak incident power density = 31 +/- 5 mW/cm(2), peak specific absorption rate (SAR) at the skin surface = 622 +/- 100 W/kg; duration 30 min daily for 3 days. MW treatment was applied to the nasal area. The mice were additionally treated with cyclophosphamide (CPA), 100 mg/kg, a commonly used immunosuppressant and anticancer drug. Four groups of animals were used in each experiment: naive control (Naive), CPA treated (CPA), CPA treated and sham exposed (CPA + Sham), and CPA treated and MW exposed (CPA + MW). MW irradiation of CPA treated mice significantly augmented the proliferation recovery process of T cells (splenocytes). A statistically significant difference (P <.05) between CPA and CPA + MW groups was observed when cells were stimulated with an antigen. On the other hand, no statistically significant difference between CPA and CPA-Sham groups was observed. Based on flow cytometry of CD4(+) and CD8(+) T cells, two major classes of T cells, we show that CD4(+) T cells play an important role in the proliferation recovery process. MW exposure restored the CD25 surface activation marker expression in CD4(+) T cells. We next examined the effector function of purified CD4(+) T cells by measuring their cytokine profile. No changes were observed after MW irradiation in interleukin-10 (IL-10) level, a Th2 type cytokine, while the level of interferon-gamma (IFN-gamma), a Th1 type cytokine was increased twofold. Our results indicate that MWs enhance the effector function of CD4(+) T cells preferentially, through initiating a Th1 type of immune response. This was further supported by our observation of a significant enhancement of tumor necrosis factor-alpha (TNF-alpha) production by peritoneal macrophage's in CPA treated mice. The present study shows MWs ameliorate the immunosuppressive effects of CPA by augmenting the proliferation of splenocytes, and altering the activation and effector functions of CD4(+) T cells.
authors.affiliation: Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Makar
authors.forename: Mahendra
authors.initials: M
authors.lastname: Logani
authors.forename: Imre
authors.initials: I
authors.lastname: Szabo
authors.forename: Marvin
authors.initials: M
authors.lastname: Ziskin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008872:Microwaves; D011829:Radiation Dosage; D013154:Spleen / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D003520:Cyclophosphamide