Y. Nishitani et al., Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis, CLIN EXP IM, 124(2), 2001, pp. 330-336
In this study, we measured the mRNA levels of adrenomedullin (AM), C-type n
atriuretic peptide, vascular endothelial growth factor, interleukin-1 beta
(IL-1 beta) and interleukin-6 (IL-6) in peripheral blood mononuclear cells
(PBMC) of 34 patients with lupus nephritis (LN) (15 active and 19 inactive)
and 30 healthy volunteers. mRNA levels were measured using a real-time qua
ntitative PCR method. Compared with healthy volunteers, IL-6 mRNA levels we
re elevated in LN patients (P < 0.005), while AM mRNA levels were decreased
(P < 0.05). Also, IL-6 mRNA levels were higher and AM mRNA levels lower in
active LN patients compared with inactive LN patients. In addition, IL-6 m
RNA levels positively correlated and AM mRNA levels negatively correlated w
ith SLE disease activity index and laboratory findings, such as blood urea
nitrogen, serum creatinine, 50% haemolytic unit of complement and urinary e
xcretion of protein over 24 h. Furthermore, IL-6 mRNA levels were negativel
y correlated with AM mRNA levels within the same LN patients. With regard t
o pathological findings, our results showed that IL-6 mRNA levels were high
er, and AM mRNA levels significantly lower in patients with a high activity
index compared to those with a low activity index. Following treatment wit
h prednisolone, IL-6 mRNA levels in active LN patients decreased and AM mRN
A levels increased to levels comparable to those in inactive LN and healthy
volunteers. In vitro studies further demonstrated that elevated IL-6 mRNA
levels in active LN patient PBMC were suppressed by the addition of adrenom
edullin. Our results suggest that an imbalance between IL-6 and AM levels m
ay play an important role in the progression of SLE, and that the mRNA leve
ls of these genes in PBMC may be used as a disease activity index for SLE.