Use of serum concentrations of interleukin-18 and monocyte chemoattractant protein-1 as prognostic indicators in primary immune-mediated hemolytic anemia in dogs

Background: The cytokine response in immune‐mediated hemolytic anemia (IMHA) is poorly characterized and correlation with outcome is unknown. Hypothesis/Objectives: To determine if cytokine activity is correlated with outcome in dogs with IMHA. Animals: Twenty dogs with primary IMHA and 6 control dogs. Methods: Prospective study on dogs with IMHA with blood sampling at admission. Serum activity of interleukin‐2 (IL‐2), IL‐4, IL‐6, IL‐7, IL‐8, IL‐10, IL‐15, IL‐18, monocyte chemoattractant protein‐1 (MCP‐1), granulocyte‐macrophage colony stimulating factor (GM‐CSF), interferon‐inducible protein‐10, interferon‐gamma, and keratinocyte chemoattractant (KC) was assessed. Results: Thirty‐day case fatality rate was 25% (5/20 dogs). Increased concentrations (median range]) of IL‐2 (45.5 ng/L 0;830] versus 0 ng/L 0;46.8]), IL‐10 (8.2 ng/L 0;60.6] versus 0 ng/L 0;88.2]), KC (1.7 μg/L 0.3;4.7] versus 0.5 μg/L 0.2;1.1]), and MCP‐1 (162 ng/L 97.6;438] versus 124 ng/L 90.2;168]) were observed in dogs with IMHA compared with controls. The cytokine profile was indicative of a mixture of pro‐ and anti‐inflammatory cytokines of various cellular origins. Cytokines/chemokines strongly associated with macrophage/monocyte activation and recruitment were significantly increased in nonsurvivors compared with survivors; IL‐15 (179 ng/L 48.0;570] versus 21.3 ng/L 0;193]), IL‐18 (199 ng/L 58.7;915] versus 37.4 ng/L 0;128]), GM‐CSF (134 ng/L 70.0;863] versus 57.6 ng/L 0;164]), and MCP‐1 (219 ng/L 135;438] versus 159 ng/L 97.6;274]), respectively. Logistic regression suggested increased IL‐18 and MCP‐1 concentrations were independently associated with mortality in this population (P<.05, Wald's type 3). Conclusions and Clinical Importance: A mixed cytokine response is present in dogs with IMHA and mediators of macrophage activation and recruitment might serve as prognostic indicators.