Increased serum levels of interferon-gamma-inducible protein 10 and monokine induced by gamma interferon in patients with haemophagocytic lymphohistiocytosis.
We measured serum interferon-gamma-inducible protein 10 (IP-10) and monokine induced by gamma interferon (MIG) levels to investigate the role of these molecules in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). Serum IP-10 and MIG levels were significantly increased in patients with active HLH compared with those of healthy controls. Serum MIG levels decreased gradually during the course of disease in a patient who recovered without therapy. On the other hand, rapid reduction of MIG and IP-10 levels was observed after chemotherapy in a patient with severe HLH. IP-10 and MIG mRNA expression was enhanced in liver and spleen, and IP-10 mRNA expression was enhanced in bone marrow in the patients, suggesting activated macrophages that infiltrated in these organs as one of the main producers of these cytokines. Serum IP-10 and MIG levels showed a significant correlation with serum IFN-gamma levels. In addition, these chemokines had a significant correlation with fever and serum LDH levels, which are clinical indicators of disease activity of HLH. These results suggest that IP-10 and MIG which are produced by activated macrophages by the stimulation of IFN-gamma, play an important role in the pathophysiology of HLH, by recruitment of activated Th1 cells into the tissues or organs.
Takada
H
H
Department of Paediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. takada@pediatr.med.kyushu-u.ac.jp
Takahata
Y
Y
Nomura
A
A
Ohga
S
S
Mizuno
Y
Y
Hara
T
T
D000208:Acute Disease; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000378:metabolism; D016022:Case-Control Studies; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D007371:Interferon-gamma / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000378:metabolism; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000276:immunology
D015415:Biomarkers; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase