Neopterin concentrations correlate inversely with hemoglobin levels in various clinical conditions. Data confirm a relationship between immune activation and inhibitory cytokines (e.g. interferon-g) and the inhibition of erythropoiesis.
Immune
activation and the anaemia associated with chronic inflammatory disorders
Fuchs D, et al. Institute for Medical Chemistry and Biochemistry,
University of Innsbruck, Austria
(Eur J Haematol 1991; 46: 65-70)
Chronic inflammatory disorders are associated with an increased risk of
patients developing anaemia. There is some evidence that cytokines released
during cell-mediated immune responses are capable of inhibiting bone marrow
haematopoiesis. In vitro, interferon gamma and tumour-necrosis factor alpha
inhibit growth of erythroid precursor cells. The mode of action of these
cytokines is probably associated with their antiproliferative capacity.
Decrease of serum iron and increase of storage iron in patients appears to
be a consequence of the defence strategy of macrophages during long-lasting
inflammatory disorders. Decreased serum iron correlates to decreased
haemoglobin concentrations. In view of this, the development of anaemia
seems likely to result from the altered iron metabolism induced by
stimulated macrophages. Low haemoglobin levels and associated hypoxia
up-regulate the release of erythropoietin, which can explain why increased
circulating erythropoietin is usually found in patients with anaemia.
Increase
of haemoglobin levels by anti-retroviral therapy is associated with a
decrease in immune activation
Sarcletti M, et al. HIV Unit, Department of Dermatology and Venereology,
Leopold-Franzens University, Innsbruck, Austria
(Eur J Haematol 2003; 70: 17-25)
We evaluated whether an
increase in haemoglobin levels in the first 6 months of effective
anti-retroviral therapy (ART) is associated with a decrease in immune
activation. To reduce confounding factors only men (n = 35) and patients
not receiving agents known to enhance haematopoiesis or patients without
diseases that might suppress haematopoiesis were included. Simultaneously
parameters of iron metabolism and cofactors for haematopoiesis were
analysed. A median baseline haemoglobin level of 139 g L-1 increased to 149
g L-1 at month 6 of ART (P < 0.001). At baseline low haemoglobin levels
were strongly associated with high neopterin concentrations (r = - 0.64, P
< 0.001), and much less correlated to high HIV-1 RNA levels (r = - 0.41,
P < 0.05) and to a lower CD4+ cell count (r = 0.33, P < 0.05). The
change of neopterin levels during the study period correlated with the
relative change in haemoglobin levels, r = - 0.35, P = 0.03, whereas no
such correlations were found for the change of HIV-1 RNA levels and the CD4
cell count. A logistic regression analysis revealed that the change of
neopterin and soluble transferrin receptors concentrations are
independently associated with an increase of haemoglobin levels of more
than 15 g L-1. Our study supports a cause-effect relationship between
immune activation and anaemia in HIV-infected patients. Treatment of
patients with ART decreases virus load, which may thereby result in
silencing of immune effector activity thus ameliorating anaemia by
reversing the anti-proliferative effects of cytokines towards erythroid
progenitors and the iron withdrawal strategy of the immune system.
Association
between immune activation, changes of iron metabolism and anaemia in
patients with HIV infection
Fuchs D, et al. Institute of Medical Chemistry and Biochemistry,
University of Innsbruck, Innsbruck, Austria
(Eur J Haematol 1993; 50: 90-4)
The pathogenesis of anaemia associated with human immunodeficiency virus infection is still far from being understood. It cannot be explained by direct effects of the virus on the haematopoietic system. Recent data suggest a role for immune activation. In a cross-sectional study we compared blood cell counts, haemoglobin and erythropoietin levels of 63 HIV-seropositive individuals with immune activation markers (interferon-gamma, serum and urine neopterin, and beta 2-microglobulin) and with parameters or iron metabolism (serum iron, transferrin, free iron binding capacity, ferritin). We found significant correlations between the concentrations of haemoglobin and the immune activation markers and erythropoietin concentrations. Additional significant correlations existed between the parameters of iron metabolism and haemoglobin levels, and ferritin correlated inversely with transferrin. In sum, low haemoglobin levels in patients were associated with enhanced cellular immune activation, as seen by increased interferon-gamma, neopterin and beta 2-microglobulin, and with changes of iron metabolism: low haemoglobin was associated with low transferrin and free iron binding capacity and high ferritin levels. Endogenous release of cytokines such as interferon-gamma-inhibiting erythropoiesis may be one underlying cause of anaemia in these patients.
See also: http://onlinepharmacycheck.com/~doc/anemia-neopterin-ua