CYTOKINE EXPRESSION IN MULTIPLE-MYELOMA AND MONOCLONAL GAMMOPATHY - ANALYSIS BY REVERSE TRANSCRIPTION POLYMERASE CHAIN-REACTION AND QUANTITATIVE PCR/

Cytokine messenger RNA expression was studied using the reverse transc ription/polymerase chain reaction in 23 patients with multiple myeloma (MM), 16 with monoclonal gammopathy of undetermined significance (MGU S), 12 with post menopausal osteoporosis (OF) and 12 normal controls. Messenger RNAs for IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta, IL-6 an d M-CSF were sought in view of their reported pathogenic role in myelo ma. Transcripts for IL-1 beta, TNF-alpha, TNF-beta and M-CSF were foun d frequently in all four groups of patients. The only significant diff erence in cytokine expression between the groups was for IL-6 which wa s expressed in 17% of controls compared with 87% of patients with MM ( p < 0.001), 62% of patients with MGUS (p < 0.02) and 67% of patients w ith osteoporosis (p < 0.02). Further analysis of IL-6 expression by qu antitative PCR showed significantly higher IL-6 mRNA levels in MM comp ared with MGUS (p < 0.006). There was no correlation however between e xpression of individual cytokines and clinical features of myeloma suc h as osteolytic bone disease or hypercalcaemia. We conclude that expre ssion of IL-6 mRNA is significantly enhanced in multiple myeloma when compared with MGUS. However, since MGUS and osteoporosis were also ass ociated with a high prevalence of IL-6 expression when compared with c ontrols it is probable that factors other than IL-6 are responsible fo r the local osteolytic lesions which characterise MM, but which are no t seen in MGUS or osteoporosis.