[The effect of combination therapy of cyclosporine with steroid on the production of gamma-interferon and interleukin-1 in kidney transplant recipients].
The present study examined the effects of CsA administered with steroid in vivo on the capacity of kidney transplant recipient mononuclear cells to generate cytokines and their gene expression at the level of messenger RNA (mRNA). Peripheral blood mononuclear cells (PBMC) from CsA-Prednisolone (Pred) treated recipients displayed 66.9% inhibition (54.3 + 12.4 IU/ml, n = 42, p less than 0.01) of gamma-IFN production compared with normal individuals (134.6 + 18.6 IU/ml, n = 23). Azathioprine (Az)-Pred treated recipients displayed significantly less inhibition of gamma-IFN generation (96.0 + 16.1 IU/ml, n = 22, p less than 0.05) than CsA treated patients. Macrophages (m phi) from CsA-Pred treated recipients displayed 60.0% inhibition (5.1 + 0.7 U/ml, n = 20, p less than 21). These result were confirmed by the experiments using cDNA probe for gamma-IFN or IL-1 (alpha, beta). High levels of gamma-IFN mRNA in PHA-stimulated PBL or IL-1 (beta) mRNA in LPS-stimulated m phi were present in normal individuals, but not in CsA treated recipients as judged by hybridization to a cloned human gamma-IFN or IL-1 (beta) cDNA probe. These studies demonstrated that combination therapy of CsA with steroid inhibits both gamma-IFN and IL-1 gene expression at the level of mRNA at physiological concentration.
Yoshimura
N
N
Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Oka
T
T
Hamashima
T
T
Lee
C J
CJ
Ohsaka
Y
Y
Hirakawa
K
K
D003524:Cyclosporins / Q000627:therapeutic use*; D015342:DNA Probes; D003864:Depression, Chemical; D004359:Drug Therapy, Combination; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism
D003524:Cyclosporins; D015342:DNA Probes; D007375:Interleukin-1; D012333:RNA, Messenger; D007371:Interferon-gamma; D011239:Prednisolone