Inflammatory response and acute phase proteins in the transition period of high-yielding dairy cows

The transition period (3 weeks before and after calving) of high-yielding dairy cows is commonly characterized by the occurrence of high disease rates, and represents the most critical phase in the production cycle. Around calving, cows usually develop a systemic inflammatory response with no signs of infections, and show lower dry matter intake and energy efficiency, as well as distinct changes of carbohydrate and fat metabolism, impaired liver capacity to metabolize the fatty acids and increased risk of liver lipidosis. The acute phase response is evident in terms of both positive (APP+: i.e. haptoglobin, ceruloplasmin, Serum Amyloid A) and negative (APP-: i.e. albumin, paraoxonase, “carriers” of vitamins and hormones, lipoproteins) acute phase proteins. The raise of APP+ synthesis in the liver partly competes with the usual synthesis of liver proteins (APP- response), which contributes – along with early metabolic and tissue distribution losses– to lower levels of such proteins, and therefore to reduced liver functions and ensuing systemic repercussions. Interestingly, cows with a severe acute phase reaction after calving period show reduced feed intake even before calving. Cows classified according to APP- levels after calving show a clear relationship with performance (i.e. cows with lower levels and/or slower recovery of APP- produce less milk and are less fertile). The above changes take place in the framework of a clear inflammatory cytokine response, distinct signs of immunosuppression and a generalized rise of intra- and extra-cellular Heat Shock Protein (HSP) 72kDa. An important role of cytokines is also demonstrated by the clear worsening of inflammatory and metabolic responses following administration of interferon alpha. The above changes start in the late pregnancy period in terms of a clear interleukin-6 (IL-6) and ceruloplasmin (APP+) response. Moreover, cows that suffer from high inflammatory conditions at the beginning of lactation show a lower energy efficiency, which is accounted for by a likely increase of the energy cost for the immune response. Interestingly, attempts to reduce inflammation around calving in apparently healthy animals by oral acetylsalicylate administration resulted in earlier resumption of liver protein synthesis (APP-) during the first month of lactation and improved performance (milk yield and fertility). Altogether, these results confirm the impact of inflammation on health and performances in dairy cows and the related consequences in terms of culling risk. The reasons for a high frequency of inflammatory response around calving in the absence of infections remain obscure. The most likely explanation is the presence of subclinical phenomena and/or different ill-defined components (i.e. genetic, epigenetic, nutritional) among high-yielding dairy cattle. In this respect, circumstantial evidence in the authors’ labs on thousands of cow serum samples showed that high-yielding Frisian dairy cows present much lower serum lisozyme contents compared with other dairy and beef cattle breeds; also, the lower lisozyme contents in lactating Frisian cows go along in our experience with inflammatory signs like high peripheral blood granulocyte counts, monocytosis and low albumin/globulin ratios. A role of lysozyme in the homeostatic regulation of the inflammatory response was actually confirmed in vitro. Therefore, the lack of an adequate homeostatic control over an otherwise innocuous inflammatory response to pregnancy and lactation onset could give rise to an early APP+ response; in turn, this might be conducive to the serious APP- response after calving, which is definitely a negative prognostic event for disease occurrence.