A proinflammatory immune response underlies impairment of intestinal barrier function in Holstein calves exposed to heat stress

Heat stress has been associated with promoting a systemic and local proinflammatory response, which could involve impaired intestinal structure and function in growing dairy calves. We hypothesized that heat stress-induced reduction of the intestinal barrier function would be associated with changes in immune cell counts, and the administration of the glucocorticoid dexamethasone would attenuate the proinflammatory response and restore intestinal barrier function. The objective of the study was to determine the effect of reducing the proinflammatory response on systemic and local immune cell concentrations, focusing on the major leukocyte types (neutrophils and lymphocytes), as well as structural and functional changes in the intestine of dairy calves exposed to heat stress. Thirty-two Holstein bull calves (n = 8/treatment) were housed in individual pens based on BW (68.5 ± 1.37 kg; mean ± SD), starter intake, and ADG determined during 2 wk before treatment allocation. Calves were allowed to adapt to facilities for 5 d before treatments started and were randomly assigned to one of 4 treatments (n = 8/treatment) in a 2 × 2 factorial arrangement of environment (thermoneutral or heat stress) and intervention (saline or dexamethasone) imposed for 5 d, as follows: (1) thermoneutral (constant ambient temperature of 20°C 24 h/d) and administration of saline, (2) thermoneutral (constant ambient temperature of 20°C 24 h/d) and administration of dexamethasone, (3) cyclic heat stress (40°C ambient temperature target from 0800 to 1900 h each day) and administration of saline, and (4) cyclic heat stress (40°C ambient temperature target from 0800 to 1900 h each day) and administration of dexamethasone. Dexamethasone (0.05 mg/kg BW) or saline (1.2 mL) was administered intramuscularly on d 1 and 3. On d 1 and 5, lactulose and mannitol were administered to assess intestinal barrier function, and blood samples were collected to measure leukocyte concentrations. On d 5, calves were euthanized, and intestinal mucosa was collected to conduct histological analysis. Lactulose-to-mannitol ratio results indicated that dexamethasone intervention against heat stress prevented impairment in the intestinal barrier function measured on d 1. Heat stress tended to reduce plasma mannitol concentrations on d 1, suggesting a flattening effect on intestinal villi. Histological analysis of the jejunum on d 5 showed that heat stress increased crypt depth, but dexamethasone intervention maintained the depth of jejunal crypts comparable to those observed in thermoneutral treatments. Heat stress and dexamethasone tended to increase blood neutrophil count, and dexamethasone tended to further elevate neutrophil count, with a more pronounced effect on d 1. During heat stress, dexamethasone decreased blood lymphocyte concentrations, with a more pronounced impact on d 1. In summary, dexamethasone inhibition of immune cell recruitment to the inflammatory site improved intestinal barrier function and structure. Changes in immune cell recruitment may be part of an underlying mechanism to alleviate and prevent the pathophysiology of heat stress in dairy cattle.