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

Abstract

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-a 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/mL 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 a-1-acid glycoprotein during an acute phase response.

Persistent Endothelial Damage after Intravenous Immunoglobulin Therapy in Kawasaki Disease

“…Elevated levels of fibrinogen in pre-IVIG would reflect inflammation, as previously reported [22]. Ferritin is known as one of the acute-phase proteins [23], and its level increases at tissue damage sites due to inflammation or tumors. In inflammation, enhancement of serum iron intake and induction of ferritin production in both the liver and reticuloendothelial cells via the activation of macrophages result in the elevation of ferritin levels.…”

Double-Fortified Salt Is Efficacious in Improving Indicators of Iron Deficiency in Female Indian Tea Pickers

“…Concurrent inflammation, reflected in elevated AGP and CRP values, can affect the interpretation of serum ferritin and body iron as indicators of iron status (22). Although 23% of participants had elevated AGP values and 5% had elevated CRP values at baseline, adjustments for inflammation to ferritin and body iron by regression or using multipliers of Thurnham et al (20) did not affect the results.…”

Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency During 24 Weeks of Exclusive Breastfeeding

“…In HIV affected populations anemia of inflammation is common, defined as presence of inflammation without iron deficiency anemia, and initiation of antiretroviral therapy may differentially impact indicators of iron status (increase TfR and Hb); thus measurement of the acute phase response to correct iron indicators for concurrent inflammation/infection is recommended for assessment of iron status. 46 With inflammation and infection, iron status indicators are distorted; plasma ferritin levels are falsely elevated and do not reflect body iron stores, while Hb levels are lowered. 46 TfR may be increased with iron deficiency anemia in the presence of inflammation; 46 but it is believed to be less sensitive to the effects of anemia of inflammation/infection than other indicators.…”

“…46 With inflammation and infection, iron status indicators are distorted; plasma ferritin levels are falsely elevated and do not reflect body iron stores, while Hb levels are lowered. 46 TfR may be increased with iron deficiency anemia in the presence of inflammation; 46 but it is believed to be less sensitive to the effects of anemia of inflammation/infection than other indicators. Previously in BAN we observed associations between inflammatory markers and TfR, ferritin and Hb 28 ; therefore, in our subsample analyses, we used methods recommended by Thurnham to mitigate the effects of the acute phase response on iron status indicators.…”