Subcutaneous injection of interleukin 12 induces systemic inflammatory responses in humans: implications for the use of IL-12 as vaccine adjuvant.
Interleukin 12 (IL-12) is a cytokine with important regulatory functions bridging innate and adaptive immunity. It has been proposed as an immune adjuvant for vaccination therapy of infectious diseases and malignancies. The inflammatory properties of IL-12 play an important role in the adjuvant effect. We studied the effect of s.c. injections of recombinant human IL-12 (rHuIL-12) in 26 patients with renal cell cancer and demonstrated dose-dependent systemic activation of multiple inflammatory mediator systems in humans. rHuIL-12 at a dose of 0.5 microg/kg induced degranulation of neutrophils with a significant increase in the plasma levels of elastase (p < 0.05) and lactoferrin (p = 0.01) at 24 h. Additionally, rHuIL-12 injection mediated the release of lipid mediators, as demonstrated by a sharp increase in the plasma secretory phospholipase A2 (sPLA2) level (p = 0.003). rHuIL-12, when administered at a dose of 0.1 microg/kg, showed minimal systemic effects. In conclusion, when IL-12 is used as an adjuvant, doses should not exceed 0.1 microg/kg, in order to avoid severe systemic inflammatory responses.
Portielje
Johanna E A
JE
Department of Medical Oncology, Erasmus Medical Center, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
Kruit
Wim H J
WH
Eerenberg
Anke J M
AJ
Schuler
Martin
M
Sparreboom
Alex
A
Lamers
Cor H J
CH
Gratama
Jan-Willem
JW
Stoter
Gerrit
G
Huber
Christoph
C
Hack
C Erik
CE
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects*; D007958:Leukocyte Count; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced* / Q000188:drug therapy; D013997:Time Factors
D000276:Adjuvants, Immunologic; D018664:Interleukin-12; D010741:Phospholipases A; D054467:Phospholipases A2