Cytokine regulation of the acute-phase protein levels in multiple myeloma.
BACKGROUND
Interleukin (IL) 6 has an important role in the regulation of acute-phase proteins (APPs) during an acute-phase response. We studied IL-6 and other cytokines to determine if they regulate serum APP levels in the same way under the condition of the aberrant, long-lasting 'acute-phase response' that occurs in patients with chronic inflammation and cancer.


METHODS
Serum levels of nine positive APPs [CRP, SAA, C1-INH, Bf, C5, C8, C9, alpha 1-acidic glycoprotein (AGP) and haptoglobin] and two negative APPs [transferrin and alpha 2-HS glycoprotein (AHSG)] were measured using immunochemical methods in 59 multiple myeloma patients and in 72 healthy control subjects. Serum IL-6 and tumour necrosis factor (TNF) alpha levels were determined by bioassays.


RESULTS
IL-6 was negatively correlated with five out of nine (C1-INH, C8, C9, AGP and haptoglobin) positive APPs but positively correlated with C-reactive protein (CRP). When patients with high and low IL-6 serum concentration were compared, CRP levels were higher, AGP and haptoglobin levels were lower in the high- than in the low-L-6 group, whereas no significant difference between the two groups was found in levels of the other positive and negative APPs. TNF-alpha levels were negatively correlated with transferrin and AHSG levels. No difference in the levels of positive APPs was observed between patients with low and high TNF-alpha serum concentration. By contrast, levels of both transferrin and AHSG were significantly lower in the high- than in the low-TNF-alpha group.


CONCLUSIONS
These findings indicate that, except for regulation of the negative APPs by TNF-alpha, the mechanism of APP regulation is different under the conditions of the short-term and the chronic, long-lasting 'acute-phase reaction'.
National Institute of Haematology and Immunology, Budapest, Hungary.
L
L
Bíró
G
G
Domján
A
A
Falus
L
L
Jakab
K
K
Cseh
L
L
Kalabay
G
G
Tarkovács
J
J
Tresch
E
E
Malle
J
J
Kramer
Z
Z
Prohászka
J
J
Jákó
G
G
Füst
A
A
Császár
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000210:Acute-Phase Reaction / Q000378:metabolism*; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D003185:Complement C8 / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D000209:Acute-Phase Proteins; D001798:Blood Proteins; D003182:Complement C5; D003185:Complement C8; D003186:Complement C9; D016207:Cytokines; D015850:Interleukin-6; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D060749:alpha-2-HS-Glycoprotein; D007371:Interferon-gamma