Effects of triphenyl phosphate on immune cells and cytokines in blood and thymus of young mice

Background As an organophosphate flame retardant, triphenyl phosphate (TPHP) has been widely used in many industries. Current research mainly focuses on the endocrine and reproductive toxicities of TPHP, but there is limited information on its immunotoxicity.

Objective This study explores the changes of immune cells in blood and thymus and cytokines in young mice exposed to TPHP.

Methods Twenty-eight young C57BL/6 mice (4 weeks old) were randomly divided into four groups, including control group, 50 mg·kg^-1 TPHP group (low dose group), 150 mg·kg^-1 TPHP group (middle dose group), and 450 mg·kg^-1 TPHP group (high dose group), with seven mice in each group. The young mice in each group were administered by gavage for consecutively 28 days, once a day, and the body weight was recorded. The blood and organs were collected to weigh and calculate organ coefficients. White blood cell (WBC) count was measured with blood analyser; counts and ratios of lymphocytes and myeloid cells in blood and of lymphocytes in thymus were detected by flow cytometry. The levels of granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin (IL)-4, IL^-1β, and IL-17 in plasma were measured by liquid protein chip technology.

Results After 13 days of TPHP exposure, the body weight of the high dose group was reduced by 11% compared with the control group (P < 0.05), and it was reduced by 12.6% after 28 days (P < 0.01). The organ coefficients of liver in all dose groups were higher than that in the control group (P < 0.05), but there were no differences in the organ coefficients of spleen, thymus, and kidney between the exposed groups and the control group (P>0.05). The WBC counts in blood in the low, middle, and high dose groups were (6.53±1.06)×10⁶ mL^-1, (6.91±1.50)×10⁶ mL^-1, and (7.30±2.00)×10⁶ mL^-1, respectively, and all were higher than that in the control group(3.61±0.51)×10⁶ mL^-1 (P < 0.01). The numbers of CD4⁺T cells, CD8⁺T cells, B cells in blood in each dose group were higher than those in the control group (P < 0.01), but the ratio of CD4⁺T cells in each dose group was lower than that in the control group (P < 0.01). The number of thymus WBC and the numbers and proportions of thymus CD4⁺T cells, CD8⁺T cells, and CD4⁺CD8⁺T cells in each dose group were not different from those in the control group (P>0.05). Only the ratio of myeloid cells in blood in the high dose group was increased by 29% compared with the control group (P < 0.05). The numbers of myeloid cells in the low, middle and high dose groups were increased by 79%, 82%, and 165% respectively compared with the control group (P < 0.01), and the plasma IL-4 level in the high dose group(0.29±0.12) ng·L^-1 was increased by 107% compared with the control group(0.14±0.04) ng·L^-1 (P < 0.05).

Conclusion TPHP exposure could increase the number of white blood cells and lymphocytes, and promote the secretion of IL-4, potentially inducing blood immune disorder.