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 and IL-6 production, decreased IL-1beta and IL-10 mRNA expression and B cell chronic lymphocytic leukemia (B-CLL) disease progression. We have now further investigated cytokine mRNA transcription in B-CLL cells and cytokine serum levels in B-CLL patients. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification of tumor necrosis factor (TNFalpha), IFNgamma, IL-6 and BCGF was equally often seen in non-progressive and progressive patients. However, 4 out of 23 non-progressive 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, whereas TNFalpha and IL-10 were detected in sera from 51 and 31 of 65 B-CLL patients, respectively. TNFalpha values were significantly high in sera from patients in stages III and IV with disease progression. TNFalpha and IL-10 were also detected in culture supernatants from in vitro stimulated B-CLL cells, whereas IFNgamma was undetectable in these cultures and rarely positive in serum. Although further investigations are required, our data and that from previous reports indicate that B-CLL-derived cytokines are involved in B-CLL disease progression.