Comparison of Urinary Cytokines after Ingestion of Cranberry Juice Cocktail in Pregnant Subjects: A Pilot Study

ABSTRACT

Our objective was to evaluate urinary cytokine excretion after daily cranberry or placebo exposure in pregnant women. Four-hour urine samples were collected from 27 pregnant women subjects who were randomized to cranberry juice cocktail or placebo in three treatment arms: A: Cranberry (C) two times daily (C, C; n = 10 pregnant); B: cranberry in the am, then placebo (P) in the pm (C, P; n = 9 pregnant); and C: placebo two times daily (P, P; n = 8 pregnant). Urinary cytokines were measured using commercially available kits. There was a statistically significant difference in interleukin (IL)-6 of the urinary cytokines between the multiple daily cranberry dosing group (group A [C, C]): median, 3.16 (range, 0.01 to 7.34) and the placebo group (group C [P, P]): 9.32 (0.53 to 29.61 pg/mL; p = 0.038, Kruskal-Wallis test). We concluded that a difference in IL-6 was found in the multiple daily cranberry dosing groups compared with placebo. Lack of differences based on treatment allocation in the other cytokines may be due to β error. Further studies are planned to evaluate these assays for the assessment of clinical effect.

KEYWORDS

Cranberry - urinary tract infection - cytokines

REFERENCES

• 1 Jepson R G, Craig J C. A systematic review of the evidence for cranberries and blueberries in UTI prevention.  Mol Nutr Food Res. 2007;  51(6) 738-745
• 2 Jepson R G, Craig J C. Cranberries for preventing urinary tract infections.  Cochrane Database Syst Rev. 2008;  (1) CD001321
• 3 Avorn J, Monane M, Gurwitz J H, Glynn R J, Choodnovskiy I, Lipsitz L A. Reduction of bacteriuria and pyuria after ingestion of cranberry juice.  JAMA. 1994;  271(10) 751-754
• 4 Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women.  Can J Urol. 2002;  9(3) 1558-1562
• 5 McMurdo M E, Bissett L Y, Price R J, Phillips G, Crombie I K. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial.  Age Ageing. 2005;  34(3) 256-261
• 6 Li Z, Seeram N P, Carpenter C L et al.. Cranberry does not affect prothrombin time in male subjects on warfarin.  J Am Diet Assoc. 2006;  106(12) 2057-2061
• 7 Lilja J J, Neuvonen P J. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam—probes of CYP2c9, VYP1A2, and CYP3A4.  Clin Pharmacol Ther. 2007;  81(6) 833-839
• 8 Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells.  Antimicrob Agents Chemother. 1989;  33(1) 92-98
• 9 Foo L Y, Lu Y, Howell A B, Vorsa N. A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli .  J Nat Prod. 2000;  63(9) 1225-1228
• 10 Howell A B, Foxman B. Cranberry juice and adhesion of antibiotic-resistant uropathogens.  JAMA. 2002;  287(23) 3082-3083
• 11 Gupta K, Chou M Y, Howell A, Wobbe C, Grady R, Stapleton A E. Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial cells.  J Urol. 2007;  177(6) 2357-2360
• 12 de Man P, van Kooten C, Aarden L, Engberg I, Linder H, Svanborg Edén C. Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection.  Infect Immun. 1989;  57(11) 3383-3388
• 13 Linder H, Engberg I, Hoschützky H, Mattsby-Baltzer I, Svanborg C. Adhesion-dependent activation of mucosal interleukin-6 production.  Infect Immun. 1991;  59(12) 4357-4362
• 14 Wing D A, Rumney P J, Preslicka C W, Chung J H. Daily cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: a randomized, controlled pilot study.  J Urol. 2008;  180(4) 1367-1372
• 15 Jepson R G, Mihaljevic L, Craig J. Cranberries for treating urinary tract infections.  Cochrane Database Syst Rev. 2000;  (2) CD001322
• 16 Howell A B, Vorsa N, Der Marderosian A, Foo L Y. Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin extracts from cranberries.  N Engl J Med. 1998;  339(15) 1085-1086
• 17 Howell A B, Reed J D, Krueger C G, Winterbottom R, Cunningham D G, Leahy M. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity.  Phytochemistry. 2005;  66(18) 2281-2291
• 18 Ahuja S, Kaack B, Roberts J. Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth medium of P-fimbriated Escherichia coli. .  J Urol. 1998;  159(2) 559-562
• 19 Gupta K, Chou M Y, Howell A, Wobbe C, Grady R, Stapleton A E. Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial cells.  J Urol. 2007;  177(6) 2357-2360
• 20 Kinney A B, Blount M. Effect of cranberry juice on urinary pH.  Nurs Res. 1979;  28(5) 287-290
• 21 Jackson B, Hicks L E. Effect of cranberry juice on urinary pH in older adults.  Home Healthc Nurse. 1997;  15(3) 198-202
• 22 Maher M A, Mataczynski H, Stefaniak H M, Wilson T. Cranberry juice induces nitric oxide-dependent vasodilation in vitro and its infusion transiently reduces blood pressure in anesthetized rats.  J Med Food. 2000;  3(3) 141-147
• 23 Raz R, Chazan B, Dan M. Cranberry juice and urinary tract infection.  Clin Infect Dis. 2004;  38(10) 1413-1419
• 24 Lee Y L, Owens J, Thrupp L, Cesario T C. Does cranberry juice have antibacterial activity?.  JAMA. 2000;  283(13) 1691
• 25 Lee Y L, Najm W I, Owens J et al.. Anti-microbial activity of urine after ingestion of cranberry: a pilot study.  Evid Based Complement Alternat Med. 2008;  , January 16 (Epub ahead of print)
• 26 Romero R, Gotsch F, Pineles B, Kusanovic J P. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury.  Nutr Rev. 2007;  65(12 Pt 2) S194-S202
• 27 La Pine T R, Hill H R. Immunomodifiers applicable to the prevention and management of infectious diseases in children.  Adv Pediatr Infect Dis. 1994;  9 37-58
• 28 Liles W C, Van Voorhis W C. Review: nomenclature and biologic significance of cytokines involved in inflammation and the host immune response.  J Infect Dis. 1995;  172(6) 1573-1580
• 29 Benson M, Jodal U, Agace W et al.. Interleukin (IL)-6 and IL-8 in children with febrile urinary tract infection and asymptomatic bacteriuria.  J Infect Dis. 1996;  174 1080-1084
• 30 Benson M, Jodal U, Andreasson A, Karlsson A, Rydberg J, Svanborg C. Interleukin 6 response to urinary tract infection in childhood.  Pediatr Infect Dis J. 1994;  13(7) 612-616
• 31 Tullus K, Fituri O, Burman L G, Wretlind B, Brauner A. Interleukin-6 and interleukin-8 in the urine of children with acute pyelonephritis.  Pediatr Nephrol. 1994;  8(3) 280-284
• 32 Ko Y C, Mukaida N, Ishiyama S et al.. Elevated interleukin-8 levels in the urine of patients with urinary tract infections.  Infect Immun. 1993;  61 1307-1314
• 33 Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K. Systemic inflammatory response to exhaustive exercise. Cytokine kinetics.  Exerc Immunol Rev. 2002;  8 6-48
• 34 Kassir K, Vargas-Shiraishi O, Zaldivar F, Berman M, Singh J, Arrieta A. Cytokine profiles of pediatric patients treated with antibiotics for pyelonephritis: potential therapeutic impact.  Clin Diagn Lab Immunol. 2001;  8(6) 1060-1063
• 35 Sheu J N, Chen M C, Lue K H et al.. Serum and urine levels of interleukin-6 and interleukin-8 in children with acute pyelonephritis.  Cytokine. 2006;  36(5-6) 276-282
• 36 Rodríguez L M, Robles B, Marugán J M, Suárez A, Santos F. Urinary interleukin-6 is useful in distinguishing between upper and lower urinary tract infections.  Pediatr Nephrol. 2008;  23(3) 429-433
• 37 Ohnishi R, Ito H, Kasajima N et al.. Urinary excretion of anthocyanins in humans after cranberry juice ingestion.  Biosci Biotechnol Biochem. 2006;  70(7) 1681-1687