Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3

Background: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to se rine. Objective: We sought to determine whether the 2 different forms of IL-3 var ied in function. These different forms are available as recombinant protein s (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/ serine 8 [rhIL-3/S8]). Methods: The erythroleukemic cell line TF-1 was incubated with varying conc entrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/ P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and as sessed for leukotrienes (LTs), IL-4, and TNF-alpha. Results: Proliferation of TF-1 cells was induced by both forms of IL-3 at 4 8 and 72 hours but to a greater degree by rhIL-3/P8, In contrast, the mean fold increase over control values of LT and IL-4 production was higher afte r priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-alph a production was greater (and reached significance only) for rhIL-3/S8. Thi s activity was independent of IgE and thus directly stimulated by IL-3. Stu dies with basophil-enriched and basophil-depleted cell preparations reveale d that LT production was evident only from the former and TNF-alpha only fr om the latter. Conclusion: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3 /P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL -3/S8 > rhIL-3/P8).