In vivo biology of recombinant interleukin-2 infusion in sheep: Cardiopulmonary manifestations of an intravascular immune-inflammatory response

Inflammation ◽  
1989 ◽  
Vol 13 (3) ◽  
pp. 267-284 ◽  
Author(s):  
Gary J. Jesmok ◽  
Robert A. Gunther
1987 ◽  
Vol 165 (3) ◽  
pp. 650-656 ◽  
Author(s):  
M J Reddehase ◽  
W Mutter ◽  
U H Koszinowski

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that in vivo application of recombinant human IL-2 (rhIL-2) can enhance the antiviral effect of a limited number of CD8+T lymphocytes, not only in prophylaxis, but also in therapy, when virus has already colonized host tissues. The observed net effect of IL-2 was consistent with the assumption of daily effector population doublings. The prospects for IL-2-supported immunotherapy of established CMV infection depend upon the tissues involved in disease. It appears that the prospects for controlling established CMV adrenalitis are less promising than for a therapy of interstitial CMV pneumonia.


Author(s):  
Carlo Riccardi ◽  
Graziella Migliorati ◽  
Antonio Giampietri ◽  
Lorenza Cannarile ◽  
Emira Ayroldi ◽  
...  

1996 ◽  
Vol 32 ◽  
pp. S5
Author(s):  
N. Finnegan ◽  
H.P. Redmond ◽  
M. Da Costa ◽  
D. Bouchier-Hayes

1994 ◽  
Vol 17 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Tetsu Shinkai ◽  
Tomohide Tamura ◽  
Tetsuro Sano ◽  
Akira Kojima ◽  
Kenji Eguchi ◽  
...  

1994 ◽  
Vol 86 (6) ◽  
pp. 671-675 ◽  
Author(s):  
Kenneth G. M. Park ◽  
Steven D. Heys ◽  
Margaret A. McNurlan ◽  
Peter J. Garlick ◽  
Oleg Eremin

1. The ‘flooding’ dose technique was used to measure rates of lymphocyte protein synthesis after infusion of [1-13C]leucine (20 atoms% enrichment, 4 g/70 kg body weight). Lymphocyte protein synthesis was measured in healthy subjects and in patients with metastatic colorectal cancer before and during infusion of recombinant interleukin-2. Rates of protein synthesis were compared with thymidine uptake in vitro and phenotypic analysis of lymphocytes. 2. The median rate of lymphocyte protein synthesis in four healthy subjects was 9% (range 7.2–11.4%/day) and in seven patients with colorectal cancer was 6.4% (range 4.2–8.2%/day). After recombinant interleukin-2 treatment the median rate of lymphocyte protein synthesis was 27.8% (range 25.2–33.7%/day). 3. The increased rates of lymphocyte protein synthesis in vivo, after recombinant interleukin-2 infusion, corresponded with increased rates of thymidine uptake and changes in the phenotypic expression of lymphocytes, but these were less consistent than the measured rates of protein synthesis. 4. It is concluded that lymphocyte activation is accompanied by a marked increase in lymphocytic protein synthesis which may have important implications for whole body protein metabolism. Furthermore, measurement of lymphocyte protein synthesis may provide a determination of lymphocyte activation in vivo.


Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1283-1289
Author(s):  
C Bello-Fernandez ◽  
C Bird ◽  
HE Heslop ◽  
DJ Gottlieb ◽  
JE Reittie ◽  
...  

Cytokine-secreting, major histocompatibility complex-unrestricted activated killer (AK) cells are toxic to a wide range of virus-infected or malignant target cells and may be generated endogenously, eg, after bone marrow transplantation, or by infusion of cytokines such as recombinant interleukin-2 (rIL-2). Although AK cells secrete cytokines such as gamma-interferon and tumor necrosis factor, which are themselves able to recruit fresh cytokine-secreting AK cells, activation in both settings is short-lived, implying the existence of homeostatic regulatory mechanisms. We now demonstrate one mechanism by which rapid homeostasis is achieved. We show that IL-4 is produced in patients with both endogenously and exogenously generated AK cells. The cytokine was detected in serum after marrow transplantation, and IL-4 transcripts appeared in circulating lymphocytes during rIL-2 infusion. Although IL-4 inhibited the induction phase of AK cell function, it had no significant inhibitory effect on the ability of AK cells from these individuals to respond to restimulation. Nonetheless, neutralization of the IL-4 induced during cell activation doubled the half-life of AK function, once activating stimuli were removed, from 18 to 44 hours and produced a 2-log increase in AK cell secretion of tumor necrosis factor and gamma-interferon. These data suggest that IL-4 induced in vivo during lymphocyte activation abbreviates AK cell responses once the triggering stimuli have been removed. Neutralization of endogenous IL-4 in vivo by appropriate monoclonal antibodies might prolong the duration of AK function.


1987 ◽  
Vol 79 (6) ◽  
pp. 1756-1763 ◽  
Author(s):  
C Weyand ◽  
J Goronzy ◽  
C G Fathman ◽  
P O'Hanley

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