Abstract
IL-12 augments many effector functions associated with T and NK cells including induction of cytotoxic activity and secretion of various cytokines. In addition, synergistic responses with IL-2 in most of the functions attributed to that cytokine make IL-12 an attractive candidate to have a potential role as an immunotherapeutic agent. We have evaluated the effect of rhIL-12 either alone or in combination with IL-2 on the generation of cytotoxic effecters from normal human bone marrow. IL-12 induced cytotoxic effecters against NK sensitive targets within 24 h of stimulation and this activity was maintained in cultures with IL-12 supplementation for up to 2 weeks tested. The decline in NK activity seen in control cultures over a period of 2 weeks was thus not observed in IL-12 stimulated cultures. In addition, a small increase was also observed in cytotoxic activity against NK resistant Daudi cell targets. IL-12, when combined with a low to intermediate dose of IL-2, led to enhancement in IL-2 induced cytotoxicity against both NK sensitive and resistant targets. However an increase in cytotoxicity against NK resistant targets was evident only after 1 week of stimulation. Cellular yield and number of hematopoietic precursors (LTC-IC, CFU-GM, BFU-e) in IL-12 stimulated cultures was comparable to or higher than control cultures at all the three time points (days 1, 7, 14) tested. In contrast, cultures stimulated with a combination of IL-12/IL-2 showed an increased number of hematopoietic precursors at day 1 followed by a marked decrease in the number of these precursors at day 7 and day 14. The several-fold higher levels of inhibitory cytokines such as IFN-γ and TNF-β detected in these combination cultures may be responsible for this biphasic behavior of hematopoietic precursors in combination cultures. Thus, IL-12 has differential effects alone or in combination with IL-2 on lymphoid and myeloid cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 365-372 |
| Number of pages | 8 |
| Journal | Bone Marrow Transplantation |
| Volume | 16 |
| Issue number | 3 |
| State | Published - 1995 |
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Keywords
- Anti-tumor cytotoxicity
- Hematopoietic progenitors
- IL-12
- IL-2
ASJC Scopus subject areas
- Hematology
- Transplantation
Cite this
Interleukin-12 (IL-12) alone or in synergistic combination with IL-2 for in vitro activation of human bone marrow : Differential effects at different time points. / Verma, U. N.; Mazumder, A.
In: Bone Marrow Transplantation, Vol. 16, No. 3, 1995, p. 365-372.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-12 (IL-12) alone or in synergistic combination with IL-2 for in vitro activation of human bone marrow
T2 - Differential effects at different time points
AU - Verma, U. N.
AU - Mazumder, A.
PY - 1995
Y1 - 1995
N2 - IL-12 augments many effector functions associated with T and NK cells including induction of cytotoxic activity and secretion of various cytokines. In addition, synergistic responses with IL-2 in most of the functions attributed to that cytokine make IL-12 an attractive candidate to have a potential role as an immunotherapeutic agent. We have evaluated the effect of rhIL-12 either alone or in combination with IL-2 on the generation of cytotoxic effecters from normal human bone marrow. IL-12 induced cytotoxic effecters against NK sensitive targets within 24 h of stimulation and this activity was maintained in cultures with IL-12 supplementation for up to 2 weeks tested. The decline in NK activity seen in control cultures over a period of 2 weeks was thus not observed in IL-12 stimulated cultures. In addition, a small increase was also observed in cytotoxic activity against NK resistant Daudi cell targets. IL-12, when combined with a low to intermediate dose of IL-2, led to enhancement in IL-2 induced cytotoxicity against both NK sensitive and resistant targets. However an increase in cytotoxicity against NK resistant targets was evident only after 1 week of stimulation. Cellular yield and number of hematopoietic precursors (LTC-IC, CFU-GM, BFU-e) in IL-12 stimulated cultures was comparable to or higher than control cultures at all the three time points (days 1, 7, 14) tested. In contrast, cultures stimulated with a combination of IL-12/IL-2 showed an increased number of hematopoietic precursors at day 1 followed by a marked decrease in the number of these precursors at day 7 and day 14. The several-fold higher levels of inhibitory cytokines such as IFN-γ and TNF-β detected in these combination cultures may be responsible for this biphasic behavior of hematopoietic precursors in combination cultures. Thus, IL-12 has differential effects alone or in combination with IL-2 on lymphoid and myeloid cells.
AB - IL-12 augments many effector functions associated with T and NK cells including induction of cytotoxic activity and secretion of various cytokines. In addition, synergistic responses with IL-2 in most of the functions attributed to that cytokine make IL-12 an attractive candidate to have a potential role as an immunotherapeutic agent. We have evaluated the effect of rhIL-12 either alone or in combination with IL-2 on the generation of cytotoxic effecters from normal human bone marrow. IL-12 induced cytotoxic effecters against NK sensitive targets within 24 h of stimulation and this activity was maintained in cultures with IL-12 supplementation for up to 2 weeks tested. The decline in NK activity seen in control cultures over a period of 2 weeks was thus not observed in IL-12 stimulated cultures. In addition, a small increase was also observed in cytotoxic activity against NK resistant Daudi cell targets. IL-12, when combined with a low to intermediate dose of IL-2, led to enhancement in IL-2 induced cytotoxicity against both NK sensitive and resistant targets. However an increase in cytotoxicity against NK resistant targets was evident only after 1 week of stimulation. Cellular yield and number of hematopoietic precursors (LTC-IC, CFU-GM, BFU-e) in IL-12 stimulated cultures was comparable to or higher than control cultures at all the three time points (days 1, 7, 14) tested. In contrast, cultures stimulated with a combination of IL-12/IL-2 showed an increased number of hematopoietic precursors at day 1 followed by a marked decrease in the number of these precursors at day 7 and day 14. The several-fold higher levels of inhibitory cytokines such as IFN-γ and TNF-β detected in these combination cultures may be responsible for this biphasic behavior of hematopoietic precursors in combination cultures. Thus, IL-12 has differential effects alone or in combination with IL-2 on lymphoid and myeloid cells.
KW - Anti-tumor cytotoxicity
KW - Hematopoietic progenitors
KW - IL-12
KW - IL-2
UR - http://www.scopus.com/inward/record.url?scp=0029166825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029166825&partnerID=8YFLogxK
M3 - Article
C2 - 8535308
AN - SCOPUS:0029166825
VL - 16
SP - 365
EP - 372
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 3
ER -