Lactoferrin and the inflammatory response.

Polyclonal antibodies were prepared to purified breast milk lactoferrin and used in an ELISA to measure plasma concentrations in investigations of various aspects of the inflammatory response. They were also used, in situ, to evaluate granulocyte lactoferrin content in disease states. The first series of studies addressed the putative role of lactoferrin in the pathogenesis of the hypoferremic, hyperferritinemic response to acute inflammation. Dissociation between the lactoferrin response and the iron related changes in rheumatoid arthritis and after alpha-interferon administration suggested that the relationship observed in acute and chronic bacterial infection may reflect coincidental effects of inflammatory cytokines. That lactoferrin does not mediate the inflammatory hypoferremic response was established by the finding that bone marrow transplant recipients, post-myeloablation, developed a hypoferremic response during septic episodes despite virtually undetectable plasma lactoferrin concentrations. The second series of investigations employed the plasma lactoferrin concentration as an index of granulocyte activation and function in a number of inflammatory conditions. Markedly increased initial plasma concentrations in acute pneumonia reflecting profound intravascular granulocyte activation were documented to predict sepsis related mortality. Plasma and granulocyte lactoferrin studies established that viral infection is associated with an acquired granulocyte lactoferrin deficiency. Plasma measurements indicated that asthmatics, even when clinically asymptomatic, have evidence of persistent granulocyte activation.