Pre-natal/juvenile chlorpyrifos exposure associated with immunotoxicity in adulthood in Swiss albino mice.
Chlorpyrifos (CPF) is a widely used agricultural organophosphorus insecticide (OP). Epidemiological studies have reported that children living in an OP contaminated environment, showed altered immune function. However, there is a paucity of experimental evidence for CPF-induced toxicity in the developmental phases of immune system. The current studies sought to ascertain the effect of CPF on the developing immune system of mice. Swiss albino dams were exposed orally with 0, 0.3, and 3.0 mg CPF/kg/day from GD12 to PND7, and then pups were directly dosed with CPF (by gavage) through PND42. One week after the final dose of CPF (i.e. on PND49), immunotoxicities in these offspring were assessed. These analyses revealed that there were increases in Foxp3+CD25+CD4+ T-regulatory (Treg) cell frequency in the spleens of 3.0 mg CPF/kg/day-exposed female mice, but not in males. In contrast, the anti-sheep red blood cells IgM response was reduced in both genders. Moreover, splenic lymphoproliferative response to phytohemagglutinin (PHA), concanavalin A (ConA), and lipopolysaccharide (LPS), as well as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 production following LPS stimulation decreased in mice of both sexes at higher CPF doses. Together, these findings suggest that developmental CPF exposure might cause immunosuppression in mice. Some of these outcomes might arise, in part, through a suppression of pro-inflammatory cytokine production and/or changes in the responsivity (specifically to mitogens) of lymphocytes in these hosts.
Immunobiology Division, CSIR-Indian Institute of Toxicology Research-CSIR-IITR, Council of Scientific and Industrial Research, Lucknow, India.
Abhishek Kumar
AK
Singh
Archana
A
Parashar
Amit Kumar
AK
Singh
Rajeev
R
Singh
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D004390:Chlorpyrifos / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004781:Environmental Exposure; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007108:Immune Tolerance; D007306:Insecticides / Q000633:toxicity*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008934:Mitogens / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007306:Insecticides; D053645:Interleukin-2 Receptor alpha Subunit; D008934:Mitogens; D004390:Chlorpyrifos