Elevated plasma levels of interleukin 1 beta, tumour necrosis factor alpha and monocyte chemotactic protein 1 are associated with pregnancy toxaemia in ewes

Abstract

Pregnancy toxaemia is a metabolic disorder that results from an inadequate energy supply to the growing maternal-fetal unit. The mechanism underlying the pathogenesis of the syndrome has not been fully clarified; however, a key role for cytokines and chemokines including interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and monocyte chemotactic protein 1 (MCP-1) has been indicated in women and experimental animals. However, information on the maternal plasma levels of IL-1 beta, TNF-alpha and MCP-1 in ewes with pregnancy toxaemia is limited. Thus, the present study was designed to determine plasma IL-1 beta, TNF-alpha and MCP-1 concentrations in ewes with severe (n=6) and mild (n=4) naturally occurring pregnancy toxaemia and in uncomplicated pregnant ewes (n=10) using enzyme-linked immunosorbent assay (ELISA). All ewes with pregnancy toxaemia had significantly lower body temperature and respiratory rate than uncomplicated pregnant ewes (p<0.05). With the highest concentrations in severe cases, heart rate, proteinuria and serum uric acid levels as well as plasma IL-1 beta, TNF-alpha and MCP-1 were significantly different among all three groups (p<0.05). The plasma concentrations of IL-1 beta in control ewes and ewes with mild and severe toxaemia were 15.81 +/- 3.90 pg/ml, 23.83 +/- 2.42 pg/ml and 34.55 +/- 8.03 pg/ml, respectively. The plasma concentrations of TNF-alpha in control ewes and ewes with mild and severe toxaemia were 7.71 +/- 1.61 pg/ml, 16.13 +/- 3.63 pg/ml, and 22.85 +/- 3.64 pg/ml, respectively. The plasma concentrations of MCP-1 in control ewes and ewes with mild and severe toxaemia were 101.70 +/- 9.86 pg/ml, 134.75 +/- 6.24 pg/ml, and 157.67 +/- 9.69 pg/ml, respectively. Moreover, plasma IL-1 beta, TNF-alpha and MCP-1 levels were positively correlated with clinical and well-establish biochemical parameters of pregnancy toxaemia, serum uric acid and proteinuria (p<0.01). Concomitant increase of plasma IL-1 beta, TNF-alpha and MCP-1 concentrations along with serum uric acid, proteinuria, and worsening of the clinical signs indicates that such cytokines are involved in the aetiopathogenesis and in perpetuation of the local and systemic inflammatory reactions in pregnancy toxaemia in ewes. Hence, plasma IL-1 beta, TNF-alpha and MCP-1 may potentially serve as markers to monitor prognosis of pregnancy toxaemia in ewes.