Cytokine expression in B-CLL in relation to disease progression and in vitro activation

Earlier, we reported an association between low in vitro and in vivo IL-1 a nd IL-6 production, decreased IL-1 beta and IL-10 m RNA express ion and B c ell chronic lymphocytic leukemia (B-CLL) disease progression. We have now f urther investigated cytokine mRNA transcription in B-CLL cells and cytokine serum revels in B-CLL patients. Reverse transcriptase polymerase chain rea ction (RT-PCR) amplification of tumor necrosis factor (TNFalpha), IFNgamma, IL-6 and BCGF was equally often seen in non-progressive and progressive pa tients. However, 4 out of 23 nonprogressive cases expressed mRNA for IL-12 while no IL-12 expression was seen in 15 progressive patients. No IL-12 was found in sera or supernatants from in vitro stimulated B-CLL cells, wherea s TNFalpha and IL-10 were detected in sera from 51 and 31 of 65 B-CLL patie nts, respectively. TNFalpha values were significantly high in sera from pat ients in stages III and IV with disease progression. TNFalpha and IL-10 wer e also detected in culture supernatants from in vitro stimulated B-CLL cell s, whereas IFNgamma was undetectable in these cultures and rarely positive in serum. Although further investigations are required, our data and that f rom previous reports indicate that B-CLL-derived cytokines are involved in B-CLL disease progression.