Circulating dopamine level, in lung carcinoma patients, inhibits proliferation and cytotoxicity of CD4+ and CD8+ T cells by D1 dopamine receptors: an in vitro analysis.
Besides cardiovascular and renal functions, the role of dopamine in periphery as an endogenous regulator of immune functions is in the limelight. In human malignancy, depression of T cell functions is known. Interestingly, recent evidences indicate significant elevation of plasma dopamine in malignancy due to stress of the disease process. Therefore, this study evaluates whether this increased plasma dopamine exerts any influence on the proliferation and cytotoxicity of CD4+ and CD8+ T cells. Patients with lung carcinoma were selected for this study due to the high prevalence rate of this kind of cancer in developing countries and also due to strong positive biochemical and psychological criteria of stress in most of the patients. Results showed significant elevation of plasma dopamine (48.6 +/- 5.1 pg/ml) in lung cancer patients than normal controls (10.2 +/- 0.9 pg/ml). In vitro dopamine concentration, simulating the plasma concentration of the patients, significantly inhibited the proliferation and cytotoxicity of T cells of these patients and also of the normal volunteers, in presence of their respective serum. The mechanism has been attributed to be D1 class of dopamine receptor mediated elevation of intracellular cAMP in these cell populations. The results may be of significance in understanding the role of peripheral dopamine as an immunomodulator in human health and diseases.
Saha
B
B
Signal Transduction and Biogenic Amines Laboratory, Chittaranjan National Cancer Institute, Research Building, 37, S.P. Mukherjee Road, Calcutta 700 026, India.
Mondal
A C
AC
Basu
S
S
Dasgupta
P S
PS
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D017447:Receptors, Dopamine D1 / Q000502:physiology*
D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D004298:Dopamine