Summary
One of the most common side effects of treatment with recombinant interleukin-2 (IL-2) is capillary leakage. Its genesis is not completely understood. The aim of the study was to determine whether capillary leakage can be monitored by means of a non-invasive conductivity technique and to study its starting point. Eight patients with advanced renal cell cancer were studied in a medium care section of the Department of Medical Oncology, University Hospital over 4 days during treatment sessions of continuous, intravenously administered IL-2 (mean dose of 15.6 × 106 IU · m−2 · day −1). The fluid shift from the intravascular to the extra- and intracellular compartments was monitored by means of noninvasive conductivity measurements. Changes in blood volume were calculated from serial erythrocyte counts. The clinical parameters of capillary leakage (oliguria, positive fluid balance, and gain in mass) were recorded. The mean gain in mass was 9% after 4 days of IL-2 treatment. The extracellular fluid volume increased significantly [46 (SD 23.2)%; P < 0.01], whereas the intracellular fluid volume did not change. The increase in blood volume (BV) amounted to 7% (P < 0.05). The decline in albumin concentration was significantly more than the increase in BV [38 (SD 4.3) %; P < 0.01], indicating capillary albumin leakage. The main changes were observed after the 2nd day of treatment. From this study, it is suggested that conductivity measurements are a suitable method to monitor capillary leakage induced by IL-2, and could be used to detect the exact onset and severity of this leakage. The leakage started within the first 24 h of treatment and was detected as a fluid shift from the intravascular to the extracellular space, while the intracellular compartment remained stable. These measurements could be useful during intervention studies with the aim of preventing this adverse effect of IL-2.
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References
Aukland K, Nicolaysen G (1981) Interstitial fluid volume: local regulatory mechanisms. Physiol Rev 61:556–43
Baars JW (1993) Interleukin-2 toxicity: mechanisms and management. In: Wagstaff J, Kluwer BV (eds) Interleukin-2: the state of the art. Dordrecht, The Netherlands, pp 45–69
Baars JW, Hack CE, Wagstaff J, Eerenberg-Belmer AJM, Wolbink GJJ, Thijs LG, Strack van Schijndel RIM, van der Vall HLJA, Pinedo HM (1992) The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2. Br J Cancer 65:96–101
Baumgartner RN, Cameron Chumlea W, Roche AF (1989) Estimation of body composition from bioelectric impedance of body segments. Am J Clin Nutr 50:221–6
Ettinghausen SE, Pini RK, Rosenberg SA (1988) Increased vascular permeability in organs mediated by system administration of lymphokine-activated killer cells and recombinant interleukin-2 in mice. J Natl Cancer Inst 80:177–88
Grocneveld ABJ, Heidendal GAK, den Hollander W, Nauta JJP, Thijs LG (1987) Noninvasive assessment of regional albumin extravasation in porcine septic shock. J Crit Care 2:245–255
Guyton AC (1991) Textbook of medical physiology, 8th edn. Saunders, Philadelphia
Kanai H, Haeno M, Sakamoto K (1982) Electrical measurement of fluid distribution in legs and arms: estimation of extra-cellular and intra-cellular fluid. IEEE Front Eng Health Care 7:273–6
Karnofsky DA, Abelman WH, Craver LF, Burchenal JH (1984) The use of nitrogen mustards in the palliative treatment of carcinoma with particular reference to bronchogenic carcinoma. Cancer 1:634–69
Kouw PM, Olthof CG, Ter Wee PM, Oe PL, Donker AJM, Schneider H, De Vries PMJM (1992) Assessment of post-dialysis dry weight: an application of the conductivity measurement method. Kidney Int 41:440–4
Mazumder A, Rosenberg SA (1984) Successful adoptive immunotherapy of established pulmonary metastases with lymphokine-activated killer cells and recombinant interleukine-2. Science 225:1487–9
McGrath BP, Tiller DJ, Horvath JS, Johnson JR (1976) Measurement of extracellular fluid volume in patients on maintenance hemodialysis. Kidney Inter 9:57–9
Meijer JH, Vries PMJM de, Goovaerts HG, Oe PL, Donker AIM, Schneider H (1989) Measurement of transcellular fluid shift during hemodialysis, I. Method. Med Biol Eng Comput 27:147–51
Mier JW, Vachino G, Klemper MS, Aronson FR, Noring R, Smith S, Brandon EP, Laird W, Atkins MB (1990) Inhibition of Interleukin-2 induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of Interleukin-2 associated side effects. Blood 76:1933–40
Olthof CG, Vries PMJM de, Kouw PM, Oe PL, Schneider H, Lange JJ de, Donker AIM (1993) Non-invasive conductivity method for detection of dynamic body fluid changes: in vitro and in vivo validation. Nephrol Dial Transplant 8:41–46
Planque BA de, Geyskes GG, Van Dongen R, Dorhout Mees EJ (1965) Simultaneous determination of extracellular volume and blood volume with the Volemetron. Clin Chim Acta 11:270–7
Rose BD (1990) Clinical physiology of acid-base and electrolyte disorders, 3rd edn, McGraw-Hill, New York
Rosenberg SA, Mule JJ, Spiess PJ, Reichert CM, Schwarz SL (1985) Regression of established pulmonary metastases and subcutaneous tumor mediated by systemic administration of high-dose recombinant interleukin 2. J Exp Med 161:1169–88
Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM et al (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukine-2 or high-dose interleukine-2 alone. N Eng J Med 316:889–97
Rosenstein M, Ettinghausen SE, Rosenberg SA (1986) Extravasation of intravascular fluid mediated by systemic administration of recombinant interleukine 2. J Immunol 137:1735–42
Segal KR, Burastero S, Chun A, Coronel P, Pierson RN, Wang J (1991) Estimation of extracellular and total body water by multiple-frequency bioclectrical-impedance measurement. Am J Clin Nutr 54:26–9
Smith KA (1988) Interleukine-2: inception, impact and implications. Science 240:1169–75
Soberman R, Brodie BB, Levy BB, Axelrod J, Hollander V, Steele JM (1949) The use of total body water in man. J Biol Chem 179:31–42
Taylor AE, Parker JC, Allison RC (1984) Capillary exchange of fluid and protein. In: Shoemaker WC, Thompson WL, Holbrook PR (eds) Textbook of critical care. Saunders, Philadelphia, pp 359–367
de Vries PMJM (1989) Determination of intracellular and extracellular fluid volume by means of non-invasive conductivity measurements. Method, in vitro validation and clinical application during haemodialysis and haemofiltration. Thesis, Free University Press, Amsterdam
de Vries PMJM, Meijer JH, Oe PL, Van Bronswijk H, Schneider H, Donker AJM (1987) Conductivity measurements for analysis of transcellular fluid shifts during hemodialysis. Trans Am Soc Artif Intern Organs 33:554–6
de Vries PMJM, Meijer JH, Vlaanderen K, Visser V, Oe PL, Donker AJM, Schneider H (1989) Measurement of transcellular fluid shift during hemodialysis, II. In vitro and clinical evaluation. Med Biol Eng Comput 27:152–8
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Olthof, C.G., Baars, J.W., Wagstaff, J. et al. Determination of capillary leakage due to recombinant interleukin-2 by means of noninvasive conductivity measurements. Europ. J. Appl. Physiol. 67, 168–173 (1993). https://doi.org/10.1007/BF00376662
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DOI: https://doi.org/10.1007/BF00376662