Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation.
Leukocyte activation is known to involve cell membrane potential changes. Phenobarbital, an anesthetic and anticonvulsant that can inhibit neuronal membrane depolarization, may also affect leukocyte activation. Measuring membrane potential, actin polymerization, chemotaxis, superoxide production, lymphocyte proliferation, intracellular calcium concentration, and cytokine production, we found that phenobarbital at a concentration of 15-30 micrograms/ml, which is considered a therapeutic serum level for controlling seizures, did not affect polymorphonuclear neutrophil (PMN) activation. At levels higher than 100 micrograms/ml, phenobarbital significantly suppressed formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis. Concentrations greater than 300 micrograms/ml also inhibited phorbol myristate acetate-stimulated membrane potential change. In contrast, 30 micrograms/ml phenobarbital significantly inhibited lymphocyte proliferation stimulated by phytohemagglutinin (PHA) and pokeweed mitogen. This concentration of phenobarbital also suppressed the increase of intracellular free calcium induced by PHA. However, only a higher concentration of phenobarbital (300 micrograms/ml) was able to inhibit PHA-induced interleukin-2 (IL-2) production and suppress the proliferation of PHA-induced IL-2 receptor-bearing lymphocytes. These results suggest that concentrations of phenobarbital associated with anticonvulsive levels do not affect PMN activation but suppress lymphocyte activation, possibly by affecting intracellular signal transduction.
Yang
K D
KD
Department of Pediatrics, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Liou
W Y
WY
Lee
C S
CS
Chu
M L
ML
Shaio
M F
MF
D000199:Actins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010634:Phenobarbital / Q000494:pharmacology*; D011108:Polymers / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016897:Respiratory Burst / Q000187:drug effects*
D000199:Actins; D016207:Cytokines; D011108:Polymers; D015375:Receptors, Interleukin-2; D002118:Calcium; D010634:Phenobarbital