Interpreting indicators of iron status during an acute phase response – lessons from malaria and human immunodeficiency virus

Iron status is influenced by inflammation when the normal control of iron metabolism is reorganized by the primary mediators of the acute phase response, tumour necrosis factor-alpha and interleukin-1. The objective of this review is to show how indices of iron status, particularly haemoglobin, serum ferritin and soluble transferrin receptor concentrations relate to changes in the acute phase proteins during inflammation. The pattern of acute phase response after elective surgery, not preceded by infection, is used to demonstrate the time course of stimulation of the acute phase proteins. The changes in the concentrations of serum acute phase protein and markers of iron status during treatment for infection are used to demonstrate inter-relationships between the indicators. In many developing countries, asymptomatic malaria and human immunodeficiency virus (HIV) are common and may affect the interpretation of iron indicators during population assessments. Malaria produces an acute phase response and relationships between acute phase protein and indices of iron status indicate an influence of inflammation in both symptomatic and asymptomatic malaria, except when the parasitaemia is less than 1000/microL of blood when ferritin appears to be unaffected. HIV-1 impacts on haemopoiesis and anaemia. Anaemia increases in severity as the disease progresses and it is often a negative prognostic indicator. However, in individuals infected with HIV there may be an atypical acute phase response in the absence of opportunistic infections. Tentative conclusions are drawn concerning the inter-relationships between ferritin and the acute phase proteins, C-reactive protein and alpha-1-acid glycoprotein during an acute phase response.