Effect of Histamine‐Receptor Antagonism on the Acute Inflammatory Response to Aerobic Cycling Exercise

Abstract

Blood flow to previously exercised muscle remains elevated for up to two hours following exercise, in response to activation of histamine receptors. Histamine also plays a significant role in the inflammatory response, increasing capillary permeability and allowing circulating cells to move in and out of tissues. Following a novel bout of exercise, there is typically an acute inflammatory response that resolves within 24–48 hours. Therefore, the purpose of this experiment was to determine if histamine receptors contribute to the acute inflammatory response following aerobic exercise in untrained individuals. We hypothesized that histamine‐receptor antagonism would decrease the inflammatory response to novel aerobic exercise. Six untrained volunteers (2F, 4M) completed 60 min of stationary cycling at 60% of their VO2peak. Volunteers completed the exercise twice, in random order, after placebo or blockade (combined oral H1/H2 histamine‐receptor antagonism with 540 mg fexofenadine and 300 mg ranitidine). Venous blood samples were collected prior to exercise and at 0, 6, 12, 24, and 48 hours after exercise. Flow cytometry (Beckman, Gallios) was utilized to quantify cell populations. A multiplex cytometric bead assay (LEGENDplex, Biolegend) was used for cytokine analysis and quantification. Following exercise, total circulating leukocytes increased from 1.70×106 ±0.29 to 3.08×106±0.58 in placebo (p<0.05) and 1.92×106±0.28 to 3.44×106±0.43% in blockade (p<0.01). Relative values of neutrophils increased from 33±1.5% to 46±1.6% in placebo (p=.13) and 36±5% to 56±2% in blockade (p<0.05). On average, total circulating leukocytes and neutrophils remained more elevated following exercise with blockade vs placebo (p<0.01). There was no effect of blockade on monocyte sub‐populations vs placebo. Following exercise, pro‐inflammatory cytokine MCP‐1 increased from 150±18pg/ml to 172±20pg/ml in placebo (p=0.18) and 151±20pg/ml to 192±13pg/ml in blockade (p<0.05). Similarly, pro‐inflammatory cytokine IL‐18 increased following exercise from 34±12pg/ml to 39±14pg/ml in placebo (p=0.21) and 35±20pg/ml to 58±13pg/ml in blockade (p<0.05). On average, MCP‐1 and IL‐18 remained more elevated following exercise with blockade vs placebo (p<0.05). Contrary to our hypothesis, the pattern of the acute inflammatory response to aerobic exercise appears to be augmented, not blunted, with histamine receptor antagonism. These data suggest that histamine receptor activation may play a complicated role in the acute inflammatory response to aerobic exercise.Support or Funding InformationSupport provided by NIH grant HL115027, AHA 17GRNT33660656, and The Eugene & Clarissa Evonuk Memorial Graduate Fellowship