Alterations in T-lymphocyte sub-set profiles and cytokine secretion by PBMC of systemic lupus erythematosus patients upon in vitro exposure to organochlorine pesticides.
Chronic exposure to organochlorine pesticides (OCP) has been suspected of causing immunoregulatory abnormalities that eventually lead to development and progression of systemic lupus erythematosus (SLE), but the role of these non-genetic stimuli has remained poorly understood. The objectives of the study were to quantify the levels of different OCP residues in the blood of SLE patients and to study the effects of in vitro treatment of peripheral blood mononuclear cells (PBMC) from these patients and healthy controls with OCP. Levels of different OCP residues in the blood were measured by gas-liquid chromatography. Isolated PBMC were treated in vitro with hexachlorocyclohexane (HCH), o,p'-dichlorodiphenyltrichloroethane (DDT), or phytohemagglutinin-M (PHA-M) for 72 h, then stained with different dye-labeled monoclonal antibodies to analyze alterations in T-lymphocytes using flow cytometry. Levels of different T(H)1 and T(H)2 cytokines were also estimated by ELISA. Significantly higher levels of p,p'-DDE and β-HCH were detected in the blood of SLE patients than in healthy controls. HCH exposure markedly increased the percentages of CD3(+)CD4(+) T-lymphocytes and expression of CD45RO(+) on CD4(+) and CD8(+) T-lymphocytes, but decreased CD4(+)CD25(+) T-lymphocytes in SLE patients. DDT exposure increased the percentages of CD3(+)CD4(+) T-lymphocytes and decreased those of CD4(+)CD25(+) T-lymphocytes in SLE patients as compared to healthy controls. No significant responsiveness of patient PBMC to PHA-M stimulation was observed indicating suppression of T-lymphocytes by these OCP. Further, both HCH and DDT decreased the levels of IL-2 and IFNγ but had no effect on IL-4 levels in SLE patients. DDT also increased significantly the levels of IL-10 in patients. It is likely that higher levels and prolonged durations of exposure to HCH and DDT may significantly influence T-lymphocyte sub-sets and cytokine expression in vivo that could lead to the development or exacerbation of SLE.
Department of Microbiology, Delhi, India.
Sajad A
SA
Dar
Shukla
S
Das
Vishnampettai G
VG
Ramachandran
Sambit N
SN
Bhattacharya
M D
MD
Mustafa
Basu D
BD
Banerjee
Prashant
P
Verma
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D002849:Chromatography, Gas; D016207:Cytokines / Q000378:metabolism*; D003634:DDT / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D001556:Hexachlorocyclohexane / Q000633:toxicity; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood / Q000633:toxicity*; D007194:India; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D010575:Pesticides / Q000097:blood / Q000633:toxicity*; D010835:Phytohemagglutinins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D018675:Toxicity Tests; D055815:Young Adult
D016207:Cytokines; D006843:Hydrocarbons, Chlorinated; C508609:IL10 protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; D007376:Interleukin-2; D008934:Mitogens; D010575:Pesticides; D010835:Phytohemagglutinins; C047876:phytohemagglutinin-M; D016753:Interleukin-10; D015847:Interleukin-4; D001556:Hexachlorocyclohexane; D007371:Interferon-gamma; D003634:DDT; C016340:o,p'-DDT