Complement activation during OKT3 treatment: a possible explanation for respiratory side effects.
Respiratory side effects that sometimes occur during treatment with anti-CD3 MAb OKT3 might result from pulmonary sequestration of activated neutrophils. Therefore, we studied complement activation in relation to activation and pulmonary sequestration of neutrophils during antirejection treatment with OKT3. In each of nine patients studied, plasma C3a-desarg and C4b/c levels increased compared with pretreatment values already in the first sample taken 15 minutes after the first dose of OKT3 (P < 0.05), with peak values at 15 and 30 minutes, respectively. Levels of neutrophil degranulation product elastase (complexed to alpha 1-antitrypsin) also increased already at 15 minutes after the first dose of OKT3 (P < 0.05), which is before elevated levels of the cytokines TNF alpha, IL-6 or IL-8 were detectable. In contrast, upon subsequent OKT3 administrations or in the control group treated with methylprednisolone, neither complement activation, cytokine release nor neutrophil degranulation occurred. In five studied patients treated with OKT3, pulmonary sequestration of radiolabeled granulocytes was observed from 3 until 15 minutes after the first dose of OKT3, together with peripheral blood granulocytopenia, which lasted at least 30 minutes. In conclusion, we demonstrate a simultaneous activation of complement and pulmonary sequestration of activated granulocytes immediately following the first dose of OKT3. These phenomena may be involved in the development of respiratory side effects complicating this therapy.
Department of Internal Medicine, University of Amsterdam, The Netherlands.
M H
MH
Raasveld
F J
FJ
Bemelman
P T
PT
Schellekens
F N
FN
van Diepen
A
A
van Dongen
E A
EA
van Royen
C E
CE
Hack
I J
IJ
ten Berge
D000328:Adult; D002449:Cell Aggregation / Q000502:physiology; D015550:Cell Degranulation; D003167:Complement Activation; D003165:Complement System Proteins / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000009:adverse effects* / Q000627:therapeutic use; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D015609:Organotechnetium Compounds; D010091:Oximes; D012120:Respiration Disorders / Q000209:etiology*; D019690:Technetium Tc 99m Exametazime
D016207:Cytokines; D016853:Muromonab-CD3; D015609:Organotechnetium Compounds; D010091:Oximes; D019690:Technetium Tc 99m Exametazime; D003165:Complement System Proteins; D008775:Methylprednisolone