Archives of

Oto-Rhino-Laryngology

Arch. Otorhinolaryngol. 225, 207-209 (1979)

9 Springer-Verlag1979

Prostaglandins in Experimental Otitis Media* Douglas M. Smith, Timothy T. K. Jung, S. K. Juhn, Norman T. Berlinger, Jonathan M. Gerrard Department of Otolaryngologyand Pediatrics,Medical School,Universityof Minnesota Minneapolis, Minnesota 55455, USA

Prostaglandine bei experimenteller Otitis media Zusammenfassung. Die Prostaglandinwerte im Serum, Plasma und Mittelohrergul3 werden beim Chinchilla mittels Radioimmuntest bestimmt. Es zeigt sich, dab Prostaglandine wahrscheinlich eine wichtige Mittlerrolle bei Entstehung einer experimentellen eitrigen Mittelohrentz/indung spielen. Sehliisselwiirter: Mittelohrentz/indung - Prostaglandine - Entz/indliche Mittlerrolle

Summary. Levels of prostaglandins in serum, plasma and middle ear effusions (MEE) in chinchilla were measured by radioimmunoassay. Higher levels of PGE 2 and PGF2, were observed in the POM group than in the SOM group. Prostaglandins appear to play important roles as a mediator of the inflammatory response in experimentally induced purulent otitis media. Key words: Otitis media - Prostaglandins -- Inflammatory mediators The pathogenesis of otitis media is a complex interaction of mechanical factors, cellular responses, and chemical mediators of inflammation. It has been suggested that prostaglandins, which are important local hormones often present in inflammatory reaction, may play a role in the pathogenesis of otitis media or in the secondary bone resorbtion seen in some cases [1, 2]. We have established two models of otitis media using the chinchilla as the experimental animal. A serous otitis media was produced by mechanical obstruction of the Eustachian tube and a purulent otitis media was produced by direct inoculation of viable S. pneumonia into the middle ear [3]. The levels of prostaglandin E 2 (PGE2) and prostaglandin F2~ (PGF2c~) were measured in middle ear effusions (MEE) obtained from both animal models, and compared with their levels in serum and plasma. *

This research was supported by PHS grant (NS14538)

Offprint requests to" Douglas M. Smith, M.D. (address see above)

0302-9530/79/0225/0207/$ 01.00

208

D.M. Smith et al.

Prostaglandin measurements were made by a modification of the radioimmunoassay method (RIA) of Jaffee [4]. Two limitations of this method should be kept in mind when interpreting the results. Antisera prepared against P G E 2 will show some cross reactivity with P G E 1, thus the P G E 2 levels reported partially reflect also the level of P G E v Since P G E I and PGE 2 have generally the same biologic actions, the specificity of this assay is adequate for this study. These radioimmunoassays measured very low but significant levels of P G E 2 and also PGF2~ in plasma. This is felt to be due to interference from a background level of nonspecific substances in plasma that interfere with prostaglandin binding to antiserum, rather than a truely low level of circulating prostaglandins [5]. Our results are summarized in Tables 1 and 2. Prostaglandin levels in MEE of infected animals were found to be very high with a preponderence of PGE v Prostaglandin levels in MEE from Eustachian tube obstructed animals were lower than the levels found in purulent otitis media group. MEE from this group closely resembles a transudate of plasma. We therefore conclude that prostaglandin levels in MEE from the early stage of serous otitis media are not significant and suggest that P G E 2 and PGF2, ~ may play little role in the pathogenesis of otitis media induced by Eustachian tube obstruction. On the other hand, both PGE 2 and PGF:~ are markedly elevated, with a preponderence of P G E 2 in MEE from infected group when compared to plasma or MEE from Eustachian tube obstruction. This significant elevation suggests that prostaglandins may play a role in the pathogenesis of purulent otitis media. Because the aggregation of platelets during the formation of serum releases prostaglandins in blood [6], and because infected MEE have a considerable cellular infiltration, it is useful to compare the serum levels to infected MEE levels. The level

Table 1. Prostaglandin concentrations (pM) in blood and middle ear effusions(MEE) in experimental otitis media

Infected MEE Obstructed MEE Plasma Serum

PGE2 (pM)

PGF2,~ (pM)

19.4 + 4.6a (11)b 1.1 _+0.4 (4) 0.3 _+0.1 (8) 3.5 _+0.2 (8)

5.0 _ 1.8 1.8 _+ 1.0 0.4 +_0.I 5.7 + 0.6

a Standard error of the means b Number of samples

Table 2. The ratio of PGE2/and PGF2~ in blood and MEE PGEJPGF2~ Infected MEE Obstructed MEE Plasma Serum

6.31 0.76 0.84 0.81

(11) (4) (8) (8)

Prostaglandins in Experimental Otitis Media

209

o f P G E 2 in infected M E E is 5.5 times higher (p < 0.02) than in serum, while PGF2~ levels were similar. This suggests a preferential elevation of P G E 2 in infected MEE. Since P G E 2 and PGFz~ are antagonists in their effects [7], this shift m a y be as important as the elevation itself. The role of prostaglandins m a y simply be as local hormones causing pain and fever to w a r n of infection in this area. T h e y m a y mediate bone resorbtion seen in chronic otitis media [1] or they m a y mediate chemotaxis [8], secretion [9], vascular permeability [10], or have an as yet unknown function. It must be remembered that we have measured only two of the m a n y prostaglandins and it is quite possible that other members of this family of acid lipid hormones are involved in the inflammatory response to middle ear infection.

References 1. Bernstein, J. M., Okazaki, T., Reisman, R. E.: Prostaglandins in middle ear effusions. Arch. Otol. 102, 257-258 (1976) 2. Jackson, R. T.: Autonomic stimulation, osmolarity, and prostaglandin effects in the eustachian tube. Ann. Otol. Rhinol. Laryngol. (Suppl.) 25, 187-193 (1973), J. Clin. Invest. 52, 398-405 (1973) 3. Juhn, S. K., Paparella, M., Kim, C.: Pathogenesis of otitis media. Ann. Otol. Rhinol. Laryngol. 86, 481--492 (1977) 4. Jaffee, B. M., Behrman, H. R., Parker, C. W.: Radioimmunoassay measurement of prostaglandins E, A, and F in human plasma. (In press) 5. Samuelson, B.: Moderator's summary. J. Rep. Med. 9, 376-377 (1972) 6. Cornette, J. C., Kirton, K. T., Barr, K. L.: Radioimmunoassay of prostaglandins. J. Rep. Med. 9, 355--360 (1972) 7. Karim, S. M. (ed.): The prostaglandins. New York: Wiley-Interscience 1972 8. McClatchey, W.: Prostaglandins and inflammation: Enhancement of monocyte chemotactic responsiveness by prostaglandin E2. Prostaglandins 12, 415-426 (1976) 9. Gerrard, J. M., Townsand, D., Studdard, S.: The influence of prostaglandin G 2 on platelet ultrastructure and platelet secretion. Am. J. Pathol. 86, 99-116 (1977) 10. Jackson, R. T., Burson, J. H.: Effect of inflammatory mediators on nasal mucosa. Arch. otolaryngol. 103, 441-444 (1977) Received May 25, 1979/Accepted June 14, 1979