PMID- 7670776
OWN - NLM
STAT- MEDLINE
DCOM- 19951018
LR  - 20220331
IS  - 0263-7103 (Print)
IS  - 0263-7103 (Linking)
VI  - 34
IP  - 7
DP  - 1995 Jul
TI  - Methotrexate action in rheumatoid arthritis: stimulation of cytokine inhibitor 
      and inhibition of chemokine production by peripheral blood mononuclear cells.
PG  - 602-9
AB  - This open label study examines whether methotrexate (MTX) treatment modulates ex 
      vivo synthesis of interleukin-1 receptor antagonist (IL-1ra), soluble tumour 
      necrosis factor receptors (sTNFR p55 and p75), interleukin-1 beta (IL-1 beta), 
      tumour necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and monocyte 
      chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells (PBMC) 
      and whether changes reflect clinical response. Significant stimulation of IL-1ra 
      and sTNFR p75 as well as inhibition of IL-8 production of PBMC were associated 
      with clinical improvement observed in patients treated with MTX. When defining 
      the characteristics of patients at study entry retrospectively in responders and 
      non-responders, a significantly lower ratio of IL-1ra:IL-1 beta production before 
      and its increase upon treatment was associated with clinical response in 13 
      patients compared to five patients not responding to MTX. In addition, clinical 
      improvement was associated with decreased synthesis of IL-1 beta, TNF-alpha and 
      IL-8 induced by bacterial lipopolysaccharide, IL-1 alpha and IL-1 beta in PBMC in 
      vitro. These findings suggest that MTX therapy reverses the inflammatory type of 
      rheumatoid arthritis (RA) blood mononuclear cells by stimulating cytokine 
      inhibitor production while inhibiting inflammatory cytokine release at the same 
      time. This may explain the powerful anti-inflammatory properties of low-dose MTX 
      as observed in most RA patients. Pretreatment determination of the IL-1ra:IL-1 
      beta ratio in PBMC may be predictive with regard to a favourable therapeutic 
      response and therefore may be useful for the selection of RA patients to be 
      treated with MTX.
FAU - Seitz, M
AU  - Seitz M
AD  - Division of Rheumatology, University Hospital, Inselspital, Bern, Switzerland.
FAU - Loetscher, P
AU  - Loetscher P
FAU - Dewald, B
AU  - Dewald B
FAU - Towbin, H
AU  - Towbin H
FAU - Rordorf, C
AU  - Rordorf C
FAU - Gallati, H
AU  - Gallati H
FAU - Baggiolini, M
AU  - Baggiolini M
FAU - Gerber, N J
AU  - Gerber NJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Rheumatol
JT  - British journal of rheumatology
JID - 8302415
RN  - 0 (Cytokines)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/blood/*drug therapy/physiopathology
MH  - Cytokines/*antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Male
MH  - Methotrexate/administration & dosage/*therapeutic use
MH  - Middle Aged
MH  - Monocytes/*physiology
EDAT- 1995/07/01 00:00
MHDA- 1995/07/01 00:01
CRDT- 1995/07/01 00:00
PHST- 1995/07/01 00:00 [pubmed]
PHST- 1995/07/01 00:01 [medline]
PHST- 1995/07/01 00:00 [entrez]
AID - 10.1093/rheumatology/34.7.602 [doi]
PST - ppublish
SO  - Br J Rheumatol. 1995 Jul;34(7):602-9. doi: 10.1093/rheumatology/34.7.602.